bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations of the tumor microenvironment (TME) in recurrent glioblastoma following apatinib in combination with temozolomide.
Authors: Zhang Junping , Ge Jingjing , Li Cheng , Xue Fengjun , Zhao Chi , Kong Chenchen , Qi Shaopei , Duan Qianqian , Zhang Qin , You Xia 
Published: July 2024

e14018 Background: Glioblastoma (GBM) is the highly malignant primary central nervous system tumor. The standard treatment for glioblastoma is maximal surgical resection followed by concomitant radiotherapy and temozolomide chemotherapy, but patient’s survival still remains poor. At present, apatinib in combination with temozolomide (TMZ) has achieved reasonable clinical efficacy in the treatment of recurrent glioblastoma (rGBM), however, there are currently no clear biomarkers related to clinical efficacy or prognosis. Methods: This retrospective study was enrolled 22 rGBMs treated with apatinib in combination with TMZ and 6 patients who received standard radiotherapy combined with TMZ and experienced recurrence. At the same time, we collected their tissue samples for RNA transcriptome analysis by the Nanostring nCounter platform. In prognosis analysis, long survival benefit is defined as a PFS≥4.2 months, and short survival benefit is defined as a PFS<4.2 months. This PFS threshold was primarily referenced from a Phase III study of bevacizumab combined with chemotherapy for rGBM. The study was approved by the institutional ethics committee of Sanbo Brain Hospital, Capital Medical University (SBNK-YJ-2021-010-02) and informed consent was also obtained from the patients. Results: The differential gene of pre and post standard chemoradiotherapy results suggest that standard treatment has reduced the expression of genes associated with tumor proliferation and up-regulated the expression of the genes associated with the immune response in rGBM. In apatinib combined TMZ patients, compared to the non-response group, the response group had significantly up-regulated expression of genes related to endothelial cells and apoptosis. Enrichment analysis revealed that signaling pathways related to cell proliferation were down-regulated in the response group. In terms of prognosis, compared with the short-survival benefit group (< 4.2 months), four tumor progression-associated genes were down-regulated in response group (≥4.2 months). Hypoxia related-genes was significantly up-regulated in the long survival benefit group. Enrichment analysis showed that genes related to cell proliferation were also down-regulated in the long-survival benefit group, while the expression of signaling pathway genes related to cell activation, and immune response was significantly up-regulated. Conclusions: Our study suggests that the combination of apatinib and TMZ may potentially provide clinical benefits in treating rGBM by modulating genes associated with cell proliferation, promoting apoptosis, regulating hypoxia, and enhancing immune response within the tumor microenvironment. Clinical trial information: NCT04814329 .
Analysis of transition metals in glioblastoma tumor and plasma samples.
Authors: Shenoy Ganesh , Kuhn Madison , Sahu Aurosman , Khristov Vladimir , Heebner Madison , Wilding Hannah E. , Clegg Taylor , Bhanja Debarati , Wade Quinn , Liermann Laura J. , Wang Dongxiang , Smith Nataliya , Khunsriraksakul Chachrit , Palsa Kondaiah , Slagle-Webb Becky , Mansouri Alireza , Zacharia Brad , Proctor Elizabeth , Connor James 
Published: July 2024

e14029 Background: Transition metals such as copper, iron, zinc, and manganese are known to play essential roles in human physiology as evidenced in conditions where these metals are dysregulated. The role of transition metals in glioblastoma biology has been largely understudied. Here we investigated whether plasma and tumor transition metal content is associated with glioblastoma patient outcomes. Methods: Transition metal content was measured in 31 glioblastoma tumor samples, 21 of which had matched plasma samples, using inductively coupled plasma mass spectroscopy (ICP-MS) or inductively coupled plasma atomic emission spectroscopy (ICP-AES). Concentrations of transition metals in plasma and tumor were then then correlated with clinical parameters including median overall survival (mOS) as well as plasma cytokines. Results: Spearman correlation analysis of transition metals in glioblastoma tumor samples found that tumor manganese and tumor zinc (R = 0.52, p = 0.0048) as well as tumor copper and tumor zinc (R = 0.36, p = 0.038) were positively correlated. Plasma transition metal content did not correlate with tumor transition metal content. Kaplan-Meier and Cox regression survival analysis between high and low expressors of each respective transition metal, separated at the median, revealed that high plasma iron content was associated with prolonged survival (median overall survival: 30.1 vs 12.4 months, P = 0.0036). Plasma from glioblastoma patients in the high plasma iron group had increased levels of IFN-β (10.91 pg/mL vs 7.43 pg/mL, P = 0.004). Plasma or tumor concentrations of copper, zinc, or manganese did not associate with survival. Conclusions: Increased plasma iron content is associated with prolonged survival as well as increased plasma IFN-β levels, suggesting a possible link between iron and immune responses in glioblastoma patients.
Impact of next generation sequencing in high grade glioma management.
Authors: Barry Simon , Mustafa Yazan Hani , McGibney Carol , Royo Laura , Higgins Martin , Mohammed Wail , Iqbal Mahzar , Lim Chris , Janssen Michael , Bermingham Niamh , Faisal Jamaluddin Muhammad , O'Sullivan Michael , Kamel Mahmoud , O'Reilly Seamus , Bambury Richard Martin , Gleeson Jack 
Published: July 2024

e14031 Background: Recent advances in genomic profiling have improved our understanding of the molecular pathogenesis of high grade gliomas. Increased availability of high-throughput Next Generation Sequencing (NGS) allows the identification of genetic alterations which could direct personalized cancer treatments for HGG patients. Methods: All patients with high grade glioma (WHO Grade ≥3 glioma by 2016 or 2022 classification) in our institution, who underwent NGS testing between 2019-2023, were identified from a prospectively maintained electronic database. NGS results, from the Oncomine Precision Assay, a multi-gene panel which tests for 50 different mutations, were collated. Medical records were systematically reviewed to collect demographic, treatment and survival data. Alterations detected on NGS were characterized using the ESMO Scale for Clinical Actionability of Molecular Targets (ESCAT). Results: 53 patient samples underwent NGS testing (34 males [64%]; 19 females [36%]). Median age at diagnosis was 52 years (range: 20-72 years). Thirty patients (57%) had an ECOG PS 1 at first clinical review. 18 tumors (34%) were found to have MGMT promoter hypermethylation. 28 patients (53%) were found to have potentially actionable alterations according to the ESCAT scale; 19 (35%) EGFR mutations (ESCAT IIIA level evidence) were detected, 5 PIK3CA (9%) mutations (ESCAT IIIA), 3 FGFR3 (6%) alterations (ESCAT IIB), 2 patients with CDK 4 (4%) copy number gain (ESCAT IIIA), 2 PTPRZ1-MET (4%) fusions (ESCAT IIIA) and 1 BRAF V600E (2%) mutation (ESCAT IB). 4 patients were found to have multiple mutations on NGS. 1 sample had insufficient tissue for analysis. 2 patients (4%) were considered for targeted therapy based on NGS results (1 BRAF V600E mutation and 1 FGFR3 alteration) but both deteriorated in advance of commencing treatment. One patient received nivolumab for MSI-H recurrent GBM (ESCAT IIIB) but progressed within 3 months of commencing treatment. Conclusions: Despite advances in our understanding of the pathogenesis of these high grade gliomas and improved awareness of molecular targets, the delivery of targeted therapy to patients with HGG remains challenging. Rapid access to targeted therapy via compassionate access programmes and improved availability and access to clinical trials for patients with rare cancers and molecular alterations, is paramount.
Beyond scalpels: A meta-analysis of robotic and laparoscopic gastrectomy in long-term oncological outcomes in gastric cancer.
Authors: Silva Caroliny , Hespanhol Larissa , Oliveira João Pedro , Silva Isadora Mamede Mendes da , Vilbert Maysa , Araújo-Filho Irami 
Published: July 2024

e16125 Background: Gastric cancer persists as a substantial worldwide health concern, serving as a prominent contributor to both the incidence and fatalities associated with cancer. In this context, robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) in patients with gastric cancer is a subject of extensive scientific investigation, reflecting the ongoing evolution of minimally invasive surgical techniques. RG has been posited as a potentially advantageous alternative to LG, as it is associated with improved precision and maneuverability, particularly in complex anatomical scenarios. Conversely, LG, with its established history and widespread adoption, is characterized by a shorter learning curve and potential cost advantages. Scientific literature suggests comparable outcomes between the two techniques, while others report divergent results in terms of operative time, blood loss, and complication rates. However, the impact of both techniques in long-term oncological outcomes remains unclear. Therefore, we aimed to perform a systematic review and meta-analysis for RG and LG for oncological outcomes in patients with gastric cancer. Methods: A systematic search was performed in PubMed, Cochrane and Embase in January 2024 for randomized controlled trials or observational studies comparing RG with LG in patients with gastric cancer. Risk ratios (RR) for binary outcomes with a 95% confidence interval (CI) were pooled and a p-value < 0.05 was considered statistically significant. Rayyan and Review Manager 5.3 software were selected, respectively, to manage the reported references and perform the statistical analysis of this study. Results: A total of 3727 results were screened, of which 13 were included in the meta-analysis, totalizing 25428 patients. There were no differences between RG and LG for 3-year overall survival (RR 1.03, 95% CI 1.00 - 1.06, I2 = 50%, p = 0.06), 3-year disease free survival (RR 1.01, 95% CI 0.95 - 1.06, I2 = 45%, p = 0.82), recurrence free survival (RR 0.51, 95% CI 0.22 - 1.20, I2 = 100%, p = 0.12), 5-year disease free survival (RR 1.02, 95% CI 0.99 - 1.05, I2 = 0%, p = 0.23), and ≥ 3-year overall survival (RR 1.02, 95% CI 1.00 - 1.05, I2 = 38%, p = 0.03). Conclusions: These findings from this comprehensive meta-analysis reveal a lack of discernible disparity between RG and LG in terms of oncological outcomes. The collective evidence suggests comparable results, emphasizing the need for continued research to refine our understanding and guide clinical decision-making in the pursuit of optimized patient care. These results contribute to the ongoing dialogue surrounding optimal treatment strategies for the assessed condition.
Updated results of perioperative PD-1 antibody toripalimab plus FLOT chemotherapy for locally advanced resectable gastric or gastro-esophageal junction adenocarcinoma: A one-arm open-table phase II trial.
Authors: Li Hongli , Ge Shaohua , Zang Fenglin , Ren Peng , Cao Fuliang , Liu Rui , Yang Yuchong , Ning Tao , Bai Ming , Wang Xia , Ji Zhi , Duan Jingjing , Liang Han , Ba Yi , Deng Ting , Deng Jingyu 
Published: July 2024

e16128 Background: Perioperative chemotherapy is the standard treatment for resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma. Immune checkpoint inhibitors have activity in advanced gastric/GEJ cancer. This trial to assess the efficacy of the addition of toripalimab to FLOT for resectable patients and explore the immune microenvironment prospectively related to treatment response of neoadjuvant immunotherapy by multiplex immunohistochemistry. Methods: This is a prospective, single-arm, investigator-initiated phase II trial. Patients with histologically confirmed, resectable, gastric and GEJ adenocarcinoma (≥ cT2 or cN+) were enrolled to receive 4 pre- and post-operative cycles of toripalimab (240mg, q2w) plus FLOT (docetaxel 50 mg/m2; oxaliplatin 85 mg/m2; leucovorin 200 mg/m2; 5-Fu 2600 mg/m2, q2w). The primary endpoint were 3-year disease-free survival rate, overall survival and pathological complete response rate (pCR). Planned sample size of 36 operated patients. if the pCR rate is greater than 16% (n = 6), an additional 20 cases will be added. Multiplex immunohistochemistry is used to quantify in situ biomarker at subcellular resolution. Results: Study accrual completed at August 2022, 55 patients were enrolled, 40M/15F, age 57 (28-76), ECOG 0 (39) and 1 (16). 4 patients had not received surgery were excluded from efficacy analysis (Three patients withdrew consent after two treatment cycles and one refused surgery after 4 cycles pre-operative treatment). Fifty-one had completely neoadjuvant treatment and received surgery. Pathological response was TRG 0/ 1/ 2/ 3 in 10/ 6/ 21/ 14 patients with pCR seen in 10 (19.6%). Major pathologic response (TRG 0 and 1) was seen in 16 (31.4%) patients. At 36.6 (17.6-57.8) months follow up, the median disease-free survival (DFS) and overall survival (OS) were not reached for all patients. DFS rate at 1, 2, and 3 year is 78.4%, 56.9%, and 54.3%. OS rate at 1, 2, and 3 year is 94.1%, 69.5%, and 65.2%. Compared with TRG 2 or 3, patients with MPR showed significant longer survival (p = 0.01). Twenty-four patients underwent immune microenvironment analysis on their pre-treatment specimens by multiplex immunohistochemisty. Compared with TRG 2 or 3 (n = 11), NK cells with positive CD56 expression in tumor parenchyma microenvironment in patients with MPR (n = 13) were significant decreased (p = 0.024). Conclusions: Perioperative toripalimab in combination with FLOT showed promising efficacy with high pCR and MPR rate in patients with resectable gastric/GEJ adenocarcinoma. MPR rate and NK cells in tumor microenvironment have a predictive on therapeutic efficacy, with deserves further study. Clinical trial information: NCT04354662 .
Preliminary data of a phase Ib/II trial evaluating the efficacy and safety of adebrelimab, camrelizumab plus apatinib as first-line therapy in patients with advanced hepatocellular carcinoma.
Authors: Long Yin , Yang Qiong , Huang Ziqi , He Xiaodong , Huang Jue , Liao Jianguo , Chen Yajin , Hu Hai , Zhang Lei 
Published: July 2024

e16221 Background: The CARES-310 study has demonstrated that the combination of the anti-PD-1 antibody camrelizumab and the VEGFR2 tyrosine kinase inhibitor apatinib exhibits improved progression-free survival (PFS) and overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC). We conducted this study to investigate whether the addition of the anti-PD-L1 antibody adebrelimab to camrelizumab and apatinib would further improve clinical outcomes. Methods: This is a prospective, phase 1b/2 clinical trial employing the i3 + 3 dose escalation design. Eligibility includes adults with unresectable or metastatic HCC, a ECOG PS of 0 or 1, a Child-Pugh score ≤ 7, and at least one measurable lesion per RECIST v 1.1. In phase 1b, patients (pts) received adebrelimab (10 mg/kg or 20 mg/kg, I.V., D1, Q3W), camrelizumab (200mg, I.V., D1, Q3W), and apatinib (250 mg orally daily). Phase 2 is a single arm, open-label trial in the first-line setting. The primary objective were dose-limiting toxicity (DLT), maximal tolerated dose (MTD), and recommended phase II dose (RP2D). With α = 0.05 and 80% power, the pts needed for stage I and total of the Simon 2-stage design was 17 and 41 pts, respectively. Results: As of 4 February 2024, 6 HCC pts progressed after or were intolerant to first-line treatment (systemic therapy ± surgical resection) were treated in 1 dose cohorts. 1 DLT occurred (Grade 3 elevated blood bilirubin increased). The RP2D was adebrelimab (10 mg/kg), camrelizumab (200mg), and apatinib (250 mg). The most common drug-related AEs were Hypertension (83.3%) and Rash (50%); and Serum amylase increased, Itching, ALT/AST increased, and Hypothyroidism (each 33.3%). Immune-related AEs were similar to those seen with other checkpoint blockade agents. No drug-related AEs led to death. 1 pts (16.7%) discontinued due to drug-related AEs. Conclusions: The combination of Adebelimumab, Camrelizumab, and Apatinib demonstrated manageable safety for unresectable HCC. Enrollment in the phase II trial is ongoing and updated clinical data will be presented. Clinical trial information: NCT05924997 .
Risk factors associated with liver cancer in all US participants.
Authors: Xiong Chenxi , Su Jing , Dong X Charlie 
Published: July 2024

e16276 Background: Liver cancer incidence rates have risen in recent years, more than tripled since 1980, and the liver cancer-caused death rates have more than doubled during the same time. The objective of this research was to identify significant risk factors (both genetic and environmental) that may contribute to the liver cancer development. Methods: The study cohort was obtained from the All of Us (AoU) population with the latest data (data cutoff date 07/01/22) of 413,457 participants. The baseline survey data, genomics data, and electronic medical data have been queried for studying the risk factors to the liver cancer. Baseline demographics, comorbidities, AUDIT-C score (positive score, defined as > = 5 for men and > = 4 for women, was considered as with high risk of alcoholic hepatitis), social determinants of health (SDoH), and genetic variants were evaluated using the logistic regression models respecting the prevalence of liver cancer. Results: The study cohort included total 254,356 participants with their EMR data, genomics data, and AUDIT-C answers (median age 55 years, 61% women, 45% from minority groups, 19% Hispanics). Among them, 1,048 patients were diagnosed liver cancer. Using the logistic regression models, SDoHs showed association with the development of liver cancer. Retired groups demonstrated higher risk (adjusted odds ratio or aOR: 1.34, 95%CI:1.09-1.67) as well as the unemployed groups (aOR: 1.19, 95%CI: 0.98-1.46). C > G variants at 22:43928847 (aOR: 1.18, 95%CI: 1-1.39), G > G variants at 22:43937814 (aOR: 1.35, 95%CI: 0.97-1.82), and G > A variants at 22:43932850 (aOR: 1.18, 95%CI: 0.99-1.39) of gene PNPLA3 were associated with higher risks. C > T variants at 19:19268740 of gene TM6SF2 demonstrated higher risks (aOR: 1.23, 95%CI: 0.97-1.54) as well. The following demographic and comorbidities factors significantly contributed to the development of liver cancer: 45 to 65 age group (aOR: 6.89, 95%CI: 4.05-13), greater than 65 (aOR: 9.99, 95%CI: 5.84-18.91), hepatitis c virus infection (aOR: 12.46, 95%CI: 10.51-14.75), diabetes with chronic complications (aOR: 1.49, 95%CI: 1.25-1.78 ), diabetes without chronic complications (aOR: 1.81, 95%CI: 1.53-1.2.14). Conclusions: This study reveals that multiple risk factors are significantly associated with the liver cancer ranging from common genetic variants, socioeconomic conditions, age, viral infection, and diabetes. Thus, it is very important to take a comprehensive approach for the liver cancer prevention.
Factors associated with surgical intervention in Native American patients with hepatocellular carcinoma.
Authors: Murugan Vikram , Becken Aidan , Bine Christopher Reese , Silberstein Peter T. 
Published: July 2024

e16279 Background: Hepatocellular carcinoma (HCC) is the prevailing type of primary liver cancer, exhibited at a higher frequency in individuals afflicted by chronic liver conditions. Past literature has demonstrated the impact certain socioeconomic factors have on the prognosis of HCC. Native American patients often face late-stage cancer diagnoses and have the lowest survival rates among racial and ethnic groups. While surgery offers potential for cure, factors related to surgical interventions in liver cancer for Native American patients remain largely unexplored. Through the NCDB, this study analyzed factors associated with surgical intervention and survival trends in Native American patients with HCC. Methods: The National Cancer Database (NCDB) was used to identify Native American patients diagnosed with Hepatocellular Carcinoma from 2004 to 2019 using the histology code 8170 and race code 03 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 27, and statistical significance was set at α = 0.05. Results: Of 1193 Native American patients included in this sample, 172 (14.4%) patients received surgical treatment for HCC, while 1021 (85.6%) patients did not receive surgical treatment for HCC. Native American patients who received surgery for HCC experienced a greater mean overall survival (90 months) when compared to the mean overall survival (24 months) in HCC Native American patients who did not receive surgical treatments (p < 0.001). When controlling for age, year of diagnosis, stage, grade, facility type and income status, receiving surgery showed an independent decrease in hazard (HR = 0.245; p < 0.05). HCC Native American patients who received surgery were more likely to be treated an at academic facility, have stage I disease, and have less aggressive tumors (grade) (p < 0.05). Native American patients who did not receive surgery were more likely to be older (62 vs 60 years old), have larger tumors, and have brain, bone, lung, and liver metastases (p < 0.05). No associations of surgical versus non-surgical treatment were seen in Charlson-Deyo score, urban or rural residence, and primary payor at diagnosis. Conclusions: Native American patients with HCC who received surgical intervention experienced improved overall survival compared to non-surgical treatment groups. Native American patients undergoing surgical intervention more often received care at academic or private institutions and had lower stages of HCC. These results follow previous trends, where cancer patients receiving adequate surgical intervention generally survive longer. Further research is needed to examine other treatment differences among Native American patients and how these findings compare across other disadvantaged groups.