bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcomes of conversion surgery following immune checkpoint inhibitors and chemotherapy in stage IV gastric cancer with peritoneal metastasis.
Authors: Liang Huayuan , Li Fengping , Zhang Huimin , Xie Qing , Zhong Rou , Huang Kaihua , Yan Xiao , Li Zhiwei , Huang Zhicheng , Hu Yanfeng , Yu Jiang , Liu Hao , Li Guoxin , Zhao Liying 
Published: January 2024

281 Background: Although anti-PD-1 antibody in combination with chemotherapy and/or targeted therapy has shown promising antitumor activity in advanced gastric adenocarcinoma (GC), the evidence of conversion therapy for initially GC with peritoneal metastasis is limited. This study aimed to clarify the clinical outcomes of conversion therapy for such patients. Methods: In this retrospective single institution cohort study, we analyzed 83 GC patients with peritoneal metastasis who received first-line anti-PD-1 antibody and chemotherapy and/or target therapy (trastuzumab) between November 2019 and June 2023. In patients who respond well to treatment, when preoperative imaging studies, multidisciplinary team discussions, and staged laparoscopy indicated the absence of peritoneal metastasis and the possibility of R0 resection, patients were offered conversion surgery. In this study, palliative surgery was not included. Patients were divided into two groups: conversion therapy group and palliative therapy group. Results: All patients underwent staging laparoscopy at their initial visit and underwent at least 2 treatment cycle, with a median follow-up time of 20.3 (16-24.6) months. Of the 83 patients, 32 patients presented a clinical response and underwent re-laparoscopy. Negative peritoneal metastasis and peritoneal cytology were confirmed in 25 patients who proceeded to undergo the conversion surgery. Compared with palliative therapy group, surgery group had a significantly better median progression-free survival (PFS) (20.3 vs 5.1 months; p < 0.001) and a prolonged median overall survival (OS) (33.4 vs 11.7 months; p < 0.001). In the surgery group, 24 (96%) of 25 patients were performed laparoscopic gastrectomy radical laparoscopic gastrectomy with more than D2 lymph node dissection (only one patient underwent open gastrectomy), 19 (76%) patients achieved R0 resection, 2 (8%) patients achieved pathologic complete response (pCR) and 4 (16%) patients reached tumor regression grade (TRG) 0-1. It was observed that patients with PCI score ≤ 2 experienced a longer median OS in comparison to those with PCI scores > 2 ( unreached vs 28.5 months, P < 0.031). And multivariate analysis associated with PFS among surgery cases identified signet ring cell carcinoma as an independent adverse prognostic factor (HR 4.66; 95% CI 1.19–18.22; p = 0.027). No serious treatment-related adverse events resulted in termination of treatment or death. Conclusions: Conversion surgery following first-line anti-PD-1 antibody in combination with chemotherapy and/or targeted therapy represented a promising treatment strategy for GC patients with peritoneal metastasis. When immunochemotherapy is effective, active second-look staging laparoscopy should be performed to clarify the possibility of conversion surgery.
Health-related quality of life (HRQOL) with pembrolizumab (pembro) plus trastuzumab (tras) and chemotherapy (chemo) in first-line HER2-positive (HER2+) advanced gastric cancer: KEYNOTE-811 trial results.
Authors: Janjigian Yelena Y. , Kawazoe Akihito , Xu Jianming , Lonardi Sara , Metges Jean-Philippe , Wyrwicz Lucjan S. , Shen Lin , Ostapenko Yuriy , Bilici Mehmet , Lowery Maeve Aine , Valderrama Adriana , Guan Yanfen , Li Kan , Shih Chie-Schin , Rha Sun Young 
Published: January 2024

286 Background: In the phase 3 KEYNOTE-811 study (NCT03615326), first-line (1L) pembro with tras + chemo (pembro arm) yielded superior PFS and improved ORR with durable responses versus placebo (pbo) with tras + chemo (pbo arm) in pts with HER2+ metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma, notably in pts with PD-L1 combined positive score (CPS) ≥1. Key prespecified exploratory HRQOL outcomes supporting these data are presented. Methods: Pts with untreated histologically or cytologically confirmed advanced HER2+ G/GEJ adenocarcinoma, measurable disease per RECIST v1.1 by investigator, and ECOG PS of 0 or 1 were randomly assigned 1:1 to receive pembro 200 mg or pbo IV every 3 weeks (Q3W) with tras + chemo (cisplatin + 5-fluorouracil or capecitabine + oxaliplatin). HRQOL was evaluated in pts who received ≥1 dose of study treatment and completed ≥1 pt-reported outcome (PRO) assessment. End points were least squares mean (LSM) change from baseline, time to deterioration (TTD), and overall improvement/stability rate in prespecified subscales of EORTC QLQ-C30, QLQ-STO22, EuroQol EQ-5D-5L. LSM changes from baseline were analyzed at wk 24 when prespecified completion and compliance rates of ~60% and 80%, respectively, were met, based on review of blinded data. Results: In the PRO analyses, 685 pts were evaluable (345 pembro with tras + chemo; 340 pbo with tras + chemo). Median time from randomization to data cutoff (May 25, 2022) was 28.4 mo (range, 9.3-42.6). Completion rates were >92% at baseline and >55% at wk 24 for all assessments in both arms. Similar changes in PRO scores from baseline to wk 24 were observed for the pembro versus pbo arms (Table). Similar percentages of pts in each arm had improved or stable scores for the EORTC QLQ-C30 GHS/QOL and physical functioning scales and EORTC QLQ-STO22 subscales. TTD was similar between arms for all prespecified subscales. Conclusions: The addition of pembro to tras + chemo did not negatively affect HRQOL during treatment. Combined with safety and efficacy data, these results support the use of pembro with tras + chemo for first-line treatment of pts with HER2+ advanced gastric cancer. Clinical trial information: NCT03615326 . [Table: see text]
Design, synthesis, and evaluation of (1E,4E,6E)-1,7-diphenyl hepta-1,4,6-trien-3-one analogues-inspired o-methoxy phenyl group as potential anti–gastric cancer agents.
Authors: Khushafah Fatehi Rashad Abdulwahab 
Published: January 2024

292 Background: Gastric cancer (GC) is a major global malignancy causing significant mortality. Most diagnoses occur at advanced stages. Current treatments involve surgery, chemotherapy, and targeted therapies. Targeted drugs face resistance and side effects. Curcumin, derived from Curcuma longa, shows promise against GC. Improved analogs addressing bioavailability have been developed. Some curcumin-based compounds with o-methoxy phenyl groups exhibit enhanced anticancer activity. We designed and synthesized (1E,4E,6E)-1,7-diphenyl hepta-1,4,6-trien-3-one analogs inspired by o-methoxy phenyl for anti-gastric cancer evaluation in vitro and in vivo. Methods: We designed and synthesized a series of analogs named (1E,4E,6E)-1,7-diphenyl hepta-1,4,6-trien-3-one analogues inspired by the o-methoxy phenyl group based on association theory. Anti-tumor activity was evaluated in vitro using gastric cancer cell lines BGC-823 and SGC-7901. Compound 2 was selected as a prime candidate based on its potency. Results: Compound 2 demonstrated potent anti-tumor effects in vitro by suppressing growth, migration, and invasion of SGC-7901 and BGC-823 cells. Impressively, it prompted cell cycle arrest at the G2/M phase and initiated apoptosis through Bax activation and caspase 3 inhibition. Moreover, in vivo trials on xenograft model nude mice validated the compound's substantial anti-gastric cancer potential while maintaining a favorable safety profile. Conclusions: A group of curcumin analogs exhibiting strong anti-gastric cancer activity was developed. The active compound 2 is capable of inhibiting the growth, colony formation, migration, and invasion of gastric cancer cells. It also arrests the cell cycle at the G2/M phase and stimulates the expression of apoptosis-related proteins, showcasing a powerful anti-gastric cancer effect in vitro. Furthermore, it demonstrates significant anti-gastric cancer activity in vivo while maintaining a favorable safety profile. Our research underscores the potential of (1E, 4E, 6E)-1,7-diphenylheptyl-1,4,6-trien-3-one analogs with o-methoxyphenyl in combatting tumors and highlights their promise as a secure anti-tumor candidate drug.
Surgical decision making in locally advanced esophageal adenocarcinoma.
Authors: Sanderfer Van Christian , Holland Alexis , Donahue Erin E. , Shea Reilly , Schwarzen Ella , Mullis Nicholas , Bellavia Sophia , Kadakia Kunal C. , Salo Jonathan C. 
Published: January 2024

299 Background: Trimodality therapy consisting of chemoradiation followed by surgery (CRT+S) is considered optimal therapy for locally advanced adenocarcinoma (ACA) of the esophagus, yet the morbidity of surgery is substantial. We used CT-derived body composition and age to categorize patients into perioperative surgical mortality risk groups. Among patients with locally advanced esophageal ACA who were treated with CRT, the benefit of surgery (CRT+S) was examined in low-risk and high-risk patients. Methods: The association of perioperative mortality with age and skeletal muscle gauge (SMG) was estimated using a group of 290 patients undergoing esophagectomy of various histologies between 2010 and 2022. CT scans were analyzed to calculate SMG as the product of skeletal muscle area and skeletal muscle density. Logistic regression models were used to evaluate the association of age and SMG with 90-day surgical mortality. Patients were classified based on their predicted probability of 90 day mortality into low and high risk groups, where high risk was defined as the highest-risk 25% of patients. This model was then applied to the study cohort of patients with ACA. Log-rank tests were used to compare overall survival by treatment (CRT vs CRT+S) in the high risk and low risk groups. Results: Of 316 patients with locally advanced ACA treated with CRT, 254 underwent surgery (CRT+S). 90-day post operative mortality in the CRT+S group was 5.1%. 74 patients were categorized as high-risk and 242 as low-risk. Among low-risk patients, 213 (88.0%) were treated with surgery (CRT+S) and had a significantly longer overall survival compared to CRT (p<0.0001), with median survival of 40.6mo (95% CI 32.3, 55.5) in the CRT+S group and 17.3mo (95% CI 13.3, 36.4) in the CRT group. Among 74 high risk patients, 41 (55.4%) were treated with surgery. We did not find a difference in overall survival between the surgical group (CRT+S) and the group treated with CRT alone (p=0.34). The median survival was 27.4mo (95% CI 15.8, 32.9) in the CRT group compared to 23.0mo (95% CI 14.7, 54.4) in the CRT+S group. Conclusions: Our retrospective study demonstrated that for low-risk patients with adenocarcinoma of the esophagus, there is a survival benefit to the addition of surgery. Conversely, we failed to detect a survival benefit to the addition of surgery in the highest-risk quartile of patients. Measurement of body composition may help identify a high-risk subset of patients with locally advanced adenocarcinoma of the esophagus who may benefit from forgoing surgery after chemoradiation.
Body composition and postoperative outcomes after minimally invasive esophagectomy.
Authors: Sanderfer Van Christian , Holland Alexis , Donahue Erin E. , Shea Reilly , Schwarzen Ella , Kadakia Kunal C. , Salo Jonathan C. 
Published: January 2024

300 Background: Esophagectomy is a complex operation associated with significant morbidity for even fit, healthy patients. Prior studies have utilized hand grip strength or muscle mass to predict postoperative esophagectomy outcomes. This study however, used skeletal muscle gauge (SMG), a CT-derived body composition measure, along with age, to classify patients into groups to summarize perioperative surgical mortality after minimally invasive esophagectomy. Methods: A total of 396 patients undergoing minimally invasive esophagectomy between 2010 and 2022 were identified. Preoperative CT scans at the L3 vertebral level were analyzed to calculate skeletal muscle gauge (SMG) as the product of skeletal muscle area and skeletal muscle density. Patient demographics, histology, treatment, and outcomes including anastomotic leak, pneumonia, prolonged ventilation, discharge destination, 30-day readmission, and 90-day mortality were collected. Patients were grouped into quartiles of SMG and by age (≥75 and <75 years). 90-day postoperative mortality for the high risk group in the bottom SMG quartile (Q1) was compared to the low-risk group in the top 3 quartiles (Q234). Results: Mean age was 62.8 years (SD 10.4). Patients were 84.4% male with 87.4% White, 10.6% Black, 1.8% Hispanic, and 0.3% Asian. Histologically, 86.4% of patients had adenocarcinoma while 11.4% had squamous cell carcinoma. Anastomotic leak occurred in 8.1%, pneumonia in 16.7%, ventilation greater than 48 hours in 20.7%, and discharge to home in 82.1% of patients. 30-day readmission occurred in 16.4% and 90-day mortality in 6.1% of patients. 8 patients did not have CT scans available. Analysis of 90-day mortality as a function of age >75 and SMG risk group showed 33.3% mortality among patients >75 in Q1 for SMG, 9.6% for patients <75 in Q1 for SMG, 5.6% for patients >75 in Q234 for SMG, and 2.2% in 264 patients <75 in Q234 for SMG for subjects who had available scan data (n = 388). Conclusions: As expected, patients with older age and lower SMG have higher mortality after esophagectomy compared to younger patients with higher SMG. Patients who are >75 years old and in the bottom SMG quartile represent a small group (27/388 = 7% of the total) which are identified as a high-risk group with a mortality of 33.3%. This study identifies a small subset of patients whose risk of surgery may outweigh the benefit, particularly in patients already treated with chemoradiation. Preoperative body composition, as measured by SMG, in combination with age can be used to predict postoperative mortality after minimally invasive esophagectomy and guide treatment decisions. [Table: see text]
Clinical outcomes of primary esophagectomy and secondary esophagectomy after endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma: A propensity-score matched analysis.
Authors: Kim Minjee , Kim Tae Jun , Lee Hyuk , Min Byung-Hoon , Lee Jun Haeng , Rhee Poong-Lyul , Kim Jae J. , Min Yang Won 
Published: January 2024

307 Background: Currently it is unknown whether secondary esophagectomy after endoscopic submucosal dissection (ESD) is comparable to primary esophagectomy considering outcomes in patients with T1 esophageal cancer. We compared short- and long- term clinical outcomes between the two groups. Methods: Primary surgery (esophagectomy) was performed in 191 patients between 2003 and 2014, and 62 patients underwent secondary surgery (esophagectomy) after ESD for T1 esophageal cancer between 2007 and 2019. Propensity matching was performed for age, sex, Charlson Comorbidity Index (CCI), location, pathology, degree of differentiation, tumor size, and invasion depth. Lymph node metastasis (LNM), overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS) and postoperative complications were compared between groups. Results: Sixty-eight patients were included after propensity score matching, LNM, OS, DSS, and RFS were comparable between the two groups. Comparing primary and secondary surgery, the respective LNM rates were 23.5% and 26.5%, 6-year OS 78.0% and 89.7%, P= 0.15; DSS were 80.4% and 96.8%, P= .057; and RFS 80.8% and 89.7%, P= .069. Multivariate analyses revealed no statistically significant differences between among LNM, OS, and RFS rates. Comparing the adverse events between the two groups, more early complications were observed in the primary surgery group than in secondary surgery group (50% vs. 20.6%, P = .021). Conclusions: Secondary surgery did not increase the risk of LNM. The long-term outcomes were comparable. Therefore, attempts to perform upfront ESD for superficial esophageal squamous cell cancers are justified.
The efficacy and safety of conversion therapy after initial systemic chemotherapy in advanced esophageal cancer with distant metastases: A multicenter retrospective observational study.
Authors: Tsuji Takayuki , Matsuda Satoru , Sato Yuta , Tanaka Koji , Tsuruta Yusuke , Watanabe Masaya , Hamai Yoichi , Nasu Motomi , Saze Zenichiro , Nakashima Yuichiro , Nomura Motoo , Yamamoto Shun , Booka Eisuke , Ishiyama Koshiro , Bamba Takeo , Sakanaka Katsuyuki , Tsushima Takahiro , TAKEUCHI HIROYA , Kato Ken , Kawakubo Hirofumi 
Published: January 2024

310 Background: Systemic chemotherapy, with or without radiation, has been the standard treatment for esophageal squamous cell carcinoma (ESCC) with distant metastasis. The increased efficacy of multimodality treatment allows for the consideration of conversion therapy with curative intent for initially unresectable ESCC after initial treatment. In the present study, we examined the safety and effectiveness of conversion therapy for ESCC. Methods: Conversion therapy was defined as surgery or chemoradiation therapy (CRT) aiming at cure after initial treatment for tumors that were initially unresectable due to distant metastasis. The patients who underwent conversion therapy for ESCC between 2011 and 2021 at participating institutions were retrospectively reviewed. Patient backgrounds, treatment outcomes, and overall survival (OS) were evaluated. Results: From 22 institutions, 149 patients were enrolled. As defined, all patients received systemic chemotherapy as an initial treatment. The distant metastatic sites in para-aortic lymph nodes/extra regional mediastinal lymph nodes/lung/liver/bone/others were 81(54%)/19 (13%)/14 (9%)/11 (7%)/4 (3%)/20 (14%), respectively. After the initial treatment, 116 patients underwent surgery and 33 patients received CRT as conversion therapy. Of 116 patients who underwent conversion surgery, the incidence rate of postoperative pneumonia/leakage/recurrent laryngeal nerve palsy was 16%/7%/6%, respectively. R0 resection was obtained in 87%. Regarding the non-hematological toxicities during conversion CRT (CTCAE grade 3 or higher), decreased appetite/dysphagia/esophagitis was 21%/15%/9%, respectively. No grade 4 or higher hematologic toxicities were observed. The 3-year OS (3y-OS) rate for all patients was 41.9%; no significant differences were found between surgery and CRT groups (43.3% vs 37.0%, p = 0.112). Pathological responders showed a significantly longer OS than non-responders (3y-OS, 56.4% vs 36.1%, p = 0.010). The distribution or number of distant metastases were not identified as prognostic factors. Conclusions: This study showed that conversion therapy for ESCC patients with distant metastasis could be conducted safely and have a favorable prognosis. Since its survival benefit would depend on the pathological response, it is important to develop an indicator to predict pathological response before surgery and carefully select appropriate candidates of conversion therapy in ESCC.
Neutrophil-to-lymphocyte ratio to predict metachronous cancer after curative resection of early gastric cancer.
Authors: Kim Sunsuk , Joo Moon Kyung , Park Jong-Jae , Kwon Chan Mi , Kim Jun Hee , Kang Ji Min , Kang Min Hyung , Lee Si Eun , Kim Won Shik , Kim Seung Han , Lee Beom Jae , Chun Hoon Jai 
Published: January 2024

313 Background: We investigate the predictive value of inflammatory markers for occurrence of metachronous cancers among patients who underwent endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) and are judged as curative resection (CR). Methods: We enrolled patients who were diagnosed as EGC and underwent ESD during 2006 and 2020. We retrospective collected data of inflammatory indexes such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and erythrocyte sediment ratio (ESR). Results: A total of 1,011 patients underwent ESD for EGC, achieved CR and were followed up more than 12 months. Among them, 86 patients had metachronous cancers (85/1011, 8.4%) during 53.4 months of follow-up. Compared with patients without metachronous cancers, those with metachronous cancers were significantly older (66.9 vs. 63.8 years, P=0.004) and had higher NLR (2.1 vs. 1.8, P=0.002), however, other inflammatory indexes such as PLR and ESR were not significantly different between two groups. Kaplan-Meier analysis showed that patients with NLR ≥ 2.0 had significantly higher possibility of metachronous cancer compared with patients with NLR < 2.0 ( P=0.049 by log rank test). After adjusting age, atrophy and Helicobacter pylori status, NLR was the only significant risk factor for metachronous cancer (odds ratio: 1.33, 95% confidence interval: 1.007-1.665, P=0.011). Conclusions: NLR may have a predictive value for occurrence of metachronous cancer after CR of EGC by ESD. Further thorough investigation is necessary to validate this outcome.
Adjuvant chemoradiotherapy (CRT) plus pembrolizumab for locally advanced esophageal squamous cell carcinoma (ESCC) with high risk of recurrence after neoadjuvant CRT plus surgery: A single-arm phase II study.
Authors: Guo Jhe-Cyuan , Huang Ta-Chen , Kuo Hung-Yang , Lin Chia-Chi , Hsu Feng-Ming , Cheng Jason C. , Huang Yen-Lin , Hsieh Min-Shu , Huang Pei-Ming , Lee Jang-Ming , Wu Shu-Ling , Hsu Chih-Hung 
Published: January 2024

320 Background: Adjuvant anti-PD-1 therapy with nivolumab has shown efficacy in reducing recurrence rates in patients with locoregional esophageal cancer including squamous cell carcinoma who achieved R0 resection but harboring pathologic residual disease following neoadjuvant CRT. However, the efficacy of adjuvant anti-PD-1 therapy in improving outcomes for patients at higher risk of recurrence, especially those with involved or close resection margin (≤1 mm), remains unclear. Methods: We conducted a phase II trial of adjuvant cisplatin (30mg/m2 IV every week for 2 cycles)-based CRT (180-200cGy per fraction for 10-13 fractions) followed by pembrolizumab (200mg IV every 3 weeks for 18 cycles) in patients with locally advanced ESCC who had high-risk recurrence features in esophagectomy tumor tissues, including involved or close margin (≤1 mm), extranodal extension (ENE) of involved lymph node, and ypN2-3, following neoadjuvant CRT (ClinicalTrials.gov Identiﬁer: NCT03322267). Primary endpoint was 1-year relapse-free survival (RFS) rate in comparison with a historical control of 32%.1 Secondary endpoints included RFS, overall survival (OS), and toxicity. Results: Between Nov 2018 and Dec 2022, we enrolled a total of 25 patients with high risk recurrence features, including margin ≤1 mm (18 patients), ENE of involved lymph node (9), and ypN2-3 (9). Majority of patients were male (88%) and current smokers (84%). The median follow-up duration was 16.5 months (95% CI 10.6-27.1). One-year RFS rate was 63.3% (95% CI 44.5-79.8). Median RFS and OS were 15.3 months (95% CI 10.2-20.4) and 38.3 months (95% CI 10.2-66.3), respectively. Any grade treatment emergent adverse events (TEAEs) occurred in 56% and 75% of patients during cisplatin-based CRT and pembrolizumab treatment, respectively. Grade 3 TEAEs were infrequent, including leukopenia (4%), pancreatitis (4%), infection (8%), and colitis (4%). There was no grade 4 TRAE. Conclusions: Adjuvant cisplatin-based CRT followed by 1-year treatment of pembrolizumab was well-tolerated, and was associated with an improved 1-year RFS rate in patients with pathologic residual disease and high risk for recurrence following trimodality therapy for locally advanced ESCC. 1. Guo JC et al: J Thorac Oncol 2015;10:1481-9. Clinical trial information: NCT03322267 .