bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short-term locally advanced gastric cancer management: A cost-effectiveness analysis.
Authors: Prasath Vishnu , Quinn Patrick L. , Arjani Simran , Li Sharon , Oliver Joseph B. , Mahmoud Omar Mee , Jaloudi Mohammed , Hajifathalian Kaveh , Chokshi Ravi 
Published: June 2023

e16065 Background: Across the nation, patients with locally advanced gastric cancer (LAGC) are managed with modalities including upfront surgery (US), neoadjuvant chemoradiation therapy (NCRT), and perioperative chemotherapy (PCT). Treatment modalities themselves are associated with adverse effects which can lead to difficulty with treatment adherence in the short-term. As preoperative therapies have demonstrated survival benefits over US, long-term outcomes are expected to vary, but it is not known if differences in adherence impacts short-term treatment outcomes. We sought to perform a decision analysis comparing costs and quality-of-life associated with short-term outcomes in the treatment of patients with LAGC to identify the most cost-effective option. Methods: We designed a decision tree model to investigate the survival and costs associated with the three utilized management modalities for T2 or higher gastric cancer in the United States: US, PCT, and NCRT. The tree described costs and treatment strategies over a six-month time horizon to incorporate the complete treatment regimen and various treatment failure points encountered during therapy. Costs were derived from 2022 Medicare reimbursement rates using the third-party payer perspective for physicians and hospitals. Effectiveness was represented using quality-adjusted life months (QALMs). One QALM equates to one month of perfect health, while zero QALMs is equivalent to death. One-way, two-way, and probabilistic sensitivity analyses were utilized to test the robustness of our findings. Results: PCT was the most cost-effective treatment modality for LAGC over US and NCRT with a cost of $40,792.16 with 4.14 QALMs. US had a cost of $55,575.57 with 4.20 QALMs. NCRT was dominated by the other options with a cost of $56,510.64 with 3.70 QALMs. Across 100,000 Monte-Carlo simulations, 55.2% of trials favored PCT and the remainder favored US (44.8%). NCRT was not favored in the probabilistic sensitivity analysis. Finally, one-way and two-way sensitivity analyses did not identify any situations where alternative treatment modalities were preferred over PCT. Conclusions: In our simulated patients with diagnosed gastric cancer, the most cost-effective treatment strategy was PCT. This further confirms the preference of this modality over others in LAGC. While US demonstrated improved QALMs over PCT, the associated cost was too great to justify the benefits. [Table: see text]
Comparison of multi-omics biomarkers via liquid biopsy in early detection of gastric cancer.
Authors: Wang Xuefei , Tang Zhaoqing , Wang Yanan , Yang Jinyu , Shi Zhongyi , Liu Dan , Zhou Qiaoxia , Xu Yu , Qiu Fujun , Gu Yuan , Min Lingqiang , Ding Chen , Zhou Peng , Sun Yihong 
Published: June 2023

e16066 Background: Effective and convenient early detection methods are still lack for gastric cancer. Liquid biopsy, by detecting cell-free DNA (cfDNA) methylation, circulating tumor DNA (ctDNA) mutation, and serum protein markers etc., may provide a non-invasive method to early detect cancer. However, head-to-head comparison of these biomarkers have not been studied. Here, we report the results of the Assessment of Early-Detection Based on Liquid Biopsy in Gastric Cancer (ASCEND-GASTRIC, NCT05224596), a case-control study to early detect gastric cancer via cfDNA methylation, ctDNA mutation, and pre-specified serum protein markers. Methods: Blood samples from gastric cancer patients were prospectively collected from the Department of General Surgery of Zhongshan Hospital, Fudan University. Blood samples from age-matched healthy controls were also prospectively collected. Blood samples were subjected to a methylation panel of ~490,000 CpG sites sequenced by the ELSA-seq, a mutation panel of ultra-deep sequenced 168 genes, and tumor protein assays. All blood samples (cancer, n=134; healthy control, n=330) were randomly assigned into the training and the test sets. Results: In the training set, cfDNA methylation and ctDNA mutation efficiently discerned cancer patients from healthy controls, while the commonly used protein markers of gastric cancer were not significantly higher in the cancer patients than in the healthy controls. In the test set, cfDNA methylation achieved 65.6% sensitivity (95% confidence interval [CI], 52.5%‒77.1%) at 96.8% specificity (95% CI, 89.9%‒100%), while ctDNA mutation exhibited lower sensitivity of 16.5% (95% CI, 9.1%‒26.5%) at 95.9% specificity (95% CI, 86.0%–99.5%). On top of the methylation-based model, the mutation-based model slightly increased sensitivity (70.7%; 95% CI, 57.3%‒81.9%) at the cost of reduced specificity (91.8%; 95% CI, 80.4%‒97.7%). Conclusions: In this study, cfDNA methylation exhibited better effectiveness than ctDNA mutation and serum protein markers in the early detection of gastric cancer. Based on cfDNA methylation, ctDNA mutation might not further provide value for the detection of gastric cancer. Our study highlights the potential clinical utility of the methylation-based early detection model for gastric cancer. A further expanded validation study is ongoing. Clinical trial information: NCT05224596 . [Table: see text]
A phase 2 study of modified chemotherapy plus pembrolizumab as perioperative therapy for stage II/IIIA esophageal squamous cell carcinoma.
Authors: Yang Bo , Xiong Qi , Song Qi , Hou Xiaobin , Wang Zhanbo 
Published: June 2023

e16081 Background: Immunotherapy plus chemotherapy has shown benefits for locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal dose, administration interval, and sequence between chemotherapy and immune checkpoint inhibitor are still elusive. In this study, we prospectively analyzed the efficacy and safety of modified chemotherapy followed by anti-programmed cell death protein 1 as perioperative therapy for stage II/IIIA ESCC. Methods: Patients with stage II/IIIA esophageal squamous cell carcinoma were eligible for this study. The patients were treated with 2 cycles of attenuated nab-paclitaxel and cisplatin (180-220mg/m2 for nab-paclitaxel, 60 mg/m2 for cisplatin) on day one and pembrolizumab (200 mg for patients weighted ≥60kg or 100 mg for patients weighted <60kg) delayed on day five every 3 weeks. Subsequently, the patients received surgery four to six weeks after the second cycle treatment followed by 2 more cycles of treatments. The primary endpoints were major pathological response rate (MPR), and the second endpoints were pathological complete response rate (pCR), DFS, safety, R0 resection rate, and OS. The last follow-up time was January 31st, 2023. Results: A total of 23 patients were enrolled in our study and received whole 4 cycles of perioperative treatment. Of the whole patients, the mean age was 57.5. The median follow-up time was 19.2 months (range: 4.1-30.1). All patients underwent surgery and received R0 resection after 2 cycles of neoadjuvant attenuated chemotherapy plus delayed pembrolizumab. Down-stage was achieved in 9 of 21 (42.8%) patients with confirmed stage pre- and post- surgery. The MPR rate was 43.5%, and pCR rate was 26.1%. Up to the last follow-up, 1 patient reported death due to brain metastases, and 4 patients experienced disease progression. The median DFS and OS were not reached. The rates of one-year DFS and OS were 88.2% (15/17) and 94.4% (17/18) respectively. 21 patients (95.5%) reported treatment-related adverse events (TRAEs), most of which were grade 1-2. Two patients reported grade 3 leukopenia, and 1 patient reported grade 4 elevated transaminases and discontinued immunotherapy after surgery. The most common TRAEs were nausea (59.1%), rash (36.4%), asthenia or fatigue (31.8%), and leukopenia (27.3%). Conclusions: Our study suggested that modified nab-paclitaxel and cisplatin followed by delayed pembrolizumab as perioperative treatment was effective and well tolerated for locally advanced ESCC. Clinical trial information: ChiCTR2000034925 . [Table: see text]
Anlotinib hydrochloride combined with tislelizumab, paclitaxel liposome, and nedaplatin regimen for preoperative neoadjuvant therapy of esophageal cancer: A single-arm, single-center, phase II exploratory clinical study.
Authors: Ma Jie , Liu Cuizhen , Laoguo Shi-xue , Zhou Huafu , Wang Yongyong , Guo Jianji , Yang Lihua , Tang Jing , Li Rong , Zeng Zhiming , Dai Lei , Mo Ning , Zeng Jie 
Published: June 2023

e16082 Background: Local recurrence and distant metastasis are important causes of high mortality in patients with locally advanced esophageal cancer. Neoadjuvant therapy combined with surgery can significantly improve the prognosis of patients with locally advanced esophageal cancer. Based on the clinical data of anlotinib (a multi-targeted tyrosine kinase inhibitors) and tislelizumab (anti-pd-1 antibodies), paclitaxel liposome (a cytotoxic anti-tumor drugs) and nedaplatin (a platinum-based anti-tumor drugs) in patients with esophageal cancer, to evaluate the efficacy and safety of anlotinib hydrochloride combined with tislelizumab, paclitaxel liposome and nedaplatin in preoperative neoadjuvant therapy for patients with stage IIB-IVA esophageal cancer. Methods: This study included 18-75 years old, ECOG PS 0-1 patients with potentially resectable stage IIB-IVA esophageal cancer with a predicted survival time of ≥12 weeks and confirmed by histopathology or cytology. Patients who met the inclusion criteria received anlotinib (oral, 12mg/d1-14,Q3W) combined with tislelizumab (intravenous drip, 200mg/d1,Q3W), paclitaxel liposome (intravenous drip, 175mg/m2/d1,Q3W) and nedaplatin (intravenous drip, 80mg/m2/d1,Q3W). After 2 cycles of neoadjuvant therapy, surgery was performed, and 4-6 weeks of chemotherapy combined with targeted immune adjuvant therapy was performed after the operation, and then Anlotinib combined with tislelizumab targeted immune maintenance therapy was performed until the disease progressed. Subjects who failed to complete at least one cycle of clinical trials according to this program due to non-experimental drug factors, and seriously violated this research program, such as: failure to follow the prescribed dose, method and course of medication, will be excluded from this study. The primary endpoint was objective response rate (ORR), and secondary endpoints included progression-free survival (PFS), R0 resection rate, and pathological complete response rate. Results: From October 2021 to February 2023, 38 patients were included in this study, and clinical data of 27 patients can be used to track and evaluate clinical efficacy. The median age of the subjects was 58.5 years (range 47-75 years). the primary study end point was an ORR of 77.8% (95% CI，61%-94.5%). Conclusions: We will strictly implement the research protocol and objectively evaluate the anti-tumor activity and safety of anlotinib hydrochloride combined with tislelizumab, paclitaxel liposome and nedaplatin regimen in the treatment of patients with stage IIB ~ IVA esophageal cancer. In order to provide a safe and reliable neoadjuvant therapy for patients with locally advanced esophageal cancer. Clinical trial information: ChiCTR2100049693 .
Effect of multi-omics analysis on tumor ecosystem during neoadjuvant dose-limiting chemotherapy combination with sequential PD-1 blockade for patients with esophageal cancer.
Authors: Song Qi , Yang Bo , Xiong Qi , Wang Zhanbo , Long Yaping , Dong Zhouhuan , Zhou Wenhao 
Published: June 2023

e16085 Background: Patients with esophageal cancer benefited from neoadjuvant chemotherapy combined with immunotherapy. However, the sequence of administration during neoadjuvant therapy remains under considerable debate. Methods: A study on 23 enrolled patients with esophageal cancer who received 2 cycles of neoadjuvant treatment of dose-limiting chemotherapy combined with sequential pembrolizumab and 2 cycles of adjuvant treatment of dose-limiting chemotherapy combined with sequential pembrolizumab was carried out. Serial plasma samples were collected and subjected to T cell receptor (TCR) sequencing. Tissues with pre- and post-neoadjuvant therapy were obtained and performed with whole-exome sequencing and transcriptome sequencing. Results: After neoadjuvant therapy, the percentage of patients with a pathological major response (MPR) was 39.1% (9/23), consisting of 21.7% (5/23) completed pathological response (cPR). TCR sequencing analysis showed that the peripheral blood-dominated TCR clones significantly augmented during the neoadjuvant treatment. Tumor mutational burden (TMB) was higher in the MPR group than in the non-MPR group at baseline. In addition, infiltrating CD8+ T cells increased and regulatory T (Treg) cells decreased in the MPR group after neoadjuvant therapy. While Treg cells increased in the non-MPR group after neoadjuvant treatment. Conclusions: Dominated TCR clones increased during the neoadjuvant limited-dose chemotherapy stage, which would contribute to sequential PD-1 blockade. Additionally, TMB, CD8+ T cells, and Treg cells are associated with clinical benefits during treatment.
The effect of inflammatory-nutri̇tional prognosti̇c scori̇ng (INPS) system on treatment response and prognosi̇s i̇n pati̇ents wi̇th locally advanced gastroesophageal juncti̇on and gastri̇c cancer wi̇th neoadjuvant systemi̇c treatment.
Authors: Keskinkilic Merve , Yalcin Femin , Gozmen Tolga , Ellidokuz Hulya , Yavuzsen Tugba , Oztop Ilhan 
Published: June 2023

e16092 Background: We aimed to reveal the prognostic value of inflammatory-nutritional prognostic score (INPS), which is a new scoring system created by using frequently used immune-nutritional markers, as a biomarker, on nutrition and immune status in patients with locally advanced GEJ and gastric cancer. Methods: Patients who were treated in Dokuz Eylul University Medical Oncology Department between 2010-2022 years and diagnosed with locally advanced GEJ and gastric cancer and receiving NACT were included in this study retrospectively. We selected the most valuable biomarkers (Albumin, ABR, CRP, CAR, De-Ritis, HALP, MLR, NLR, PLR, PNI, SII) to develop INPS by the least absolute shrinkage and selection operator (LASSO) Cox regression model. A prognostic nomogram incorporating INPS and other independent clinicopathological factors was developed based on the stepwise multivariate Cox regression method. The retained features with nonzero coefficients were used to establish a novel INPS. The selected four biomarkers were used to construct the novel INPS for our patients. Results: Median follow-up time of 101 patients was 16.7 months (95% CI= 3.7-73.7), DFS was 20.5 months (95%CI= 16.2-24.8 ), OS was 36.6 months (95%CI=25.4-47.8). The 101 patients in the study were randomly assigned to train (n = 71) and test (n = 30) sets in a 7:3 ratio. Using the LASSO Cox regression model, four inflammatory-nutritional biomarkers (INB) with nonzero coefficients, namely, PLR, DeRitis, PNI and LAR, of the 13 parameters were selected. The LASSO coefficient profiles of the 13 INB and 10-fold cross-validation for tuning parameter selection in the LASSO model were presented. The optimal cut-off values for these four biomarkers based on disease-free survival were determined using the Maximally Selected Rank Statistics. The respective cut-off values for PLR, DeRitis, PNI, and LAR were obtained to be 107.93, 1.75, 33.92, and 58.17. Both the patients in the Train set and the in the Test set were classified as low-risk (INPS score ≤ 1) and high-risk (INPS score >1) groups. There was a statistically significant difference in survival probabilities between low and high risk groups in both groups (respectively; p=0.009, p=0.029). A prognostic nomogram including INPS and other independent clinicopathological factors was developed. Conclusions: The search for biomarkers with prognostic value in GEJ and gastric adenocarcinoma receiving NACT continues. With this study, it has been shown for the first time in the literature that the new screening system, INPS, created with nutritional and inflammatory markers, can be used as a prognostic tool to predict disease-free survival in this patient group.
Outcomes of patients with oesophageal and gastric cancer in relation to their age and metropolitan residential status: A South Australian audit.
Authors: Kalapurackal Mathai Vinod , Bull Jeff A , Ullah Shahid , Karapetis Christos Stelios , Watson David I. , Bright Tim F , Roy Amitesh Chandra 
Published: June 2023

e16095 Background: The incidence of oesophago-gastric cancer (OG) is increasing in the younger population. Factors such as obesity, chronic gastroesophageal reflux disease, smoking or a low dietary intake of fruits and vegetables may be responsible. Inferior survival outcomes are observed in younger patients with OG cancer. Survival rates can differ by geographic location, with poorer outcomes seen in remote and non-metropolitan regions. Aim To evaluate patient characteristics and outcomes of patients with gastro-oesophageal cancers in younger (<50 years) when compared to older (>50 years) patients and those residing in rural versus metropolitan areas in South Australia. Methods: Data from a tertiary referral hospital database in South Australia was retrospectively collected between 2012 to 2022. All patients with OG cancers were included. Baseline characteristics including demographics, risk factors for OG cancer, type and stages of disease, geographic location were collected. Survival outcomes of gastro oesophageal cancer patients <50 years and >50 years of age as well as those living in metropolitan versus rural locations were analysed. Statistical analyses were done using Pearson’s Chi square test, Wilcoxon rank sum test, Fisher exact tests and multivariate models. Results: Of the 937 patients in this audit, 6.5%% (n=61) were < 50 years of age, 72% men (n=670), median age of diagnosis was 72 years. There was statistically significant difference in the proportion of patients with different anatomical types of OG cancer based on age <50 versus >50 (P=0.02), while there was no difference in other baseline characteristics. Within the group of OG cancer patients <50 years, the frequency of gastric adenocarcinoma was more, when compared to older, >50 year group (55.7% vs 31.3%) whilst other cancer types such as GOJ adenocarcinoma (1.6% vs 6.3%), oesophageal squamous (8.2% vs 14.8%) and adenocarcinoma (34.4% vs 47.6%) were found less frequent in <50 year group compared to >50 year group. There were no significant differences observed in the 3 year (P=0.49), 5 year (P=0.61) and overall survival (2.29 vs 1.78 years, P=0.63) rates, in OG cancer patients < 50 years vs > 50 years old. Among 874 OG cancer patients with data available on geographic location, there was no significant differences observed between 3-year (P = 0.25), 5-year (P =0.27) or overall survival (1.72 vs 1.61 years, P = 0.3) in metropolitan versus rural patients in South Australia. Conclusions: In this audit gastric adenocarcinoma was more common in younger patients (<50 years of age). Young-onset OG cancer patients, when defined as aged younger than 50 years, had equivalent survival compared with their older counterparts and there were no significant differences seen in overall survival rates based on their geographic locations.
The impact of cancer prehabilitation on psychological outcomes and quality of life in patients with gastro-oesophageal cancer.
Authors: Halliday Laura , Moorthy Krishna , King Alex , Wynter-Blyth Venetia , Zamora Talaya Bernarda Zamora 
Published: June 2023

e16096 Background: The impact of cancer on psychological health and health related quality of life (HRQoL) is complex and involves an interaction between pre-existing and cancer related psychological morbidity and symptoms. Factors such as self-efficacy are known predictors of recovery and HRQoL. The aim of this study is to assess the impact of multi-modal personalised prehabilitation on psychological outcomes and HRQoL in patients with curable oesophageal and gastric (OG) cancer. Methods: Data was collected for to all patients treated at a specialist centre between Jan 2016 and June 2018. Patients received multi-modal (physical, nutrition and psychological) prehabilitation from diagnosis into the post-operative period. Data on self-efficacy (SE), anxiety and depression (Hospital Anxiety and Depression Scale, HADS) and HRQoL (European Organization for Research and treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)) were collected at diagnosis (T1), completion of neo-adjuvant chemotherapy (T2) and 3 months after surgery (T3). A previously validated mapping function was used for predicting Euro QoL 5D-3L (EQ-5D-3L) from scale scores of the EORTC QLQ-C30 instrument to derive a EQ health utility (EQ-HU). Results: 137 patients underwent surgery. 86 patients underwent a thoracotomy in addition to a laparotomy. 107 patients received neo-adjuvant treatment. There was a significant improvement in SE [8.2 (6.2-9) to 8.8 (7.8-9.7); p = 0.002] and anxiety [5 (3-8) to 4 (2,7); p = 0.04] but not depression [2 (1-5) to 3 (1-5); p = 0.26] between T1 and T2. There were no differences between T2 and T3. There were no differences in global HRQoL and the individual scales of the EORTC QLQ-C30 between T1 and T2. However, between T2 and T3, there were significant reductions in global HRQoL [69.6 (18.2) to 64.7 (20.9); p = 0.04], physical [83.2 (18.2) to 70.9 (20.5); p = 0.001], role [79 (28.6) to 70.9 (28.3; p = 0.02], cognitive [84.2 (22.3) to 76 (23.3); p = 0.004] and social [79 (24.2) to 65.5 (26.1); p = 0.001] but not emotional functions [80.1 (21.4) to 79.5 (23.3); p = 0.67]. Mapping revealed that there was a significant improvement in EQ-HU from T1 to T2 [0.54 (0.52) to 0.79 (0.34); p = 0.001] and a significant fall from T2 to T3 [ 0.79 (0.34) to 0.58 (0.44); p = 0.001]. The minimum and maximum predicted values matched those of the validated mapping function used. Conclusions: This study shows that prehabilitation can have a significant impact on HU in patients on chemotherapy. Despite the well-recognised limitations of mapping, HU at baseline was comparable to that shown in previous research in OG cancer patients. Reduction in HRQoL seen after surgery was much less than previously published research, suggesting the protective effect of prehabilitation. Physical function deterioration, in particular was much less than anticipated.