bluuebunny/crossref_metadata_2025_split huggingface dataset:
PD-1 inhibitor combined with ablation in liver metastasis: A retrospective, multicenter study.
Authors: Liu Dengyao , Huang Tao , Sun Zhanguo , Hu Pan , Zhu Tao , Huang Dongcun , Xu Bingchen , Jiao Dechao , Zhang Fujun , Lin Letao 
Published: June 2024

e14644 Background: This study aimed to retrospectively evaluate the efficacy of ablation combined with programmed cell death protein 1 (PD-1) inhibitor versus PD-1 inhibitor monotherapy in patients with liver metastasis. Methods: We retrospectively enrolled patients with liver metastasis who received PD-1 inhibitor therapy with or without ablation at three medical institutions between January 2017 and September 2022. Progression-free survival (PFS) and 1-year survival rates were compared after propensity score matching. Additionally, intrahepatic and extrahepatic lesion progression and treatment-related adverse events were recorded during follow-up. Finally, prognostic factors for the combined therapy group were analyzed. Results: We included 172 patients and classified them into the combined therapy and PD-1 inhibitor monotherapy (n = 86 each) groups. Patients in the combined therapy group had better median PFS and 1-year survival rates than those in the PD-1 inhibitor monotherapy group. Combined therapy was an independent prognostic factor for PFS in the univariate and multivariate analyses. New lesions constituted the main pattern of progression, with combined therapy showing significantly lower intrahepatic progression, but similar extrahepatic progression rates. Adverse events associated with PD-1 inhibitors were comparable between the two groups. Additionally, 8 (9.3%) patients experienced ablation-related complications. However, neither univariate, nor multivariate analyses revealed the predictive factors for PFS in the combined therapy group. Conclusions: Ablation combined with a PD-1 inhibitor was superior to PD-1 inhibitor monotherapy in improving the survival of patients with liver metastasis.
Unraveling the role of CTLA-4 variants in acute kidney injury after ICI treatments.
Authors: Wang Yanfei , Xiong Chenxi , Bian Jiang , Song Qianqian , Su Jing 
Published: June 2024

e14682 Background: Immune checkpoint inhibitors (ICIs) often result in various immune-related adverse events (irAEs), which limit their therapeutic application and pose challenges to clinical decision-making. Among these irAEs, the incidence rate of ICI-related acute kidney injury (ICI-AKI) is on the rise. Understanding the genetic predisposition to ICI-AKI can inform personalized treatment plans, thereby minimizing risks and optimizing outcomes. This study aims to interrogate risk loci for AKI patients to gain insights into ICI-related AKI in cancer patients and to support the design of more personalized cancer therapies. Methods: This study comprehensively integrates meta-analysis, replication genome-wide association study (GWAS), fine-mapping, and mendelian randomization (MR) to explore potential genetic variants related with ICI-AKI. We first conducted a meta-analysis of 6 ICI pharmacogenomics studies, aggregating effect sizes from these studies using both fixed-effect and random-effects models to address heterogeneity and identified 186 significant genotypes. Subsequently, a GWAS was carried out over the 186 candidate genotypes in an independent cohort from the NIH All of Us program (N = 230,013) using logistic regression, identifying14,773 patients who developed AKI. To identify causal variants, we implemented fine-mapping techniques to further refine our genotype selection. Results: Our study identified genetic variants associated with an increased risk of AKI. Among these, the variant with the strongest association was located at the cytotoxic T lymphocyte antigen 4 (CTLA-4) gene locus, rs3087243 (chr2: 203874196, G>A,T). This genotype exhibited a significant inverse relationship with AKI risk (beta = -8.19e-2, P = 2e-11), suggesting that reduced activity of the CTLA-4 gene may be linked to an elevated risk of developing AKI. Our findings indicate that cancer patients with this genotype may have a lower risk of ICI-related AKI after immunotherapy. In our future study, we will continue investigating significant SNPs including rs3087243 in cancer patients for their ICI-AKI risk. Conclusions: We identified an AKI-tolerant genotype, rs3087243. Patients with this genotype may be safter from developing ICI-related AKI after immunotherapy treatment. This work also highlights the research potential of All of Us clinicogenomics data.
Comparison of efficacy of antibody drug conjugate (ADCs) between younger and older patients: A meta-analysis of phase 3 studies.
Authors: Landre Thierry , Baldini Capucine , Bringuier Michael , Frelaut Maxime , Zelek Laurent H. , Taleb Cherifa 
Published: June 2024

e15002 Background: Antibody-Drug-Conjugates (ADCs) are one of the new cornerstone of cancer treatments. New approvals are coming every year in various tumor types and settings. However, older adults remain underrepresented in clinical trials and consequently, few data is available for this population. Therefore, we performed a meta-analysis to compare the efficacy of ADCs between younger and older patients. Methods: PubMed and the ASCO or ESMO databases were searched up to December 2023. We included randomized controlled trials (RCTs) of ADCs (datopotamab deruxtecan, Enfortumab vedotin, mirvetuximab soravtansine, sacituzumab govitecan and trastuzumab deruxtecan) reporting subgroup comparison of overall survival (OS) and/or progression-free survival (PFS) based on age cutoffs. The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated. Results: A total of 4654 patients from nine RCTs (ASCENT; DESTINY-Breast02, -Breast04, -Gastric01; EV-301, EV-302/KEYNOTE-A39; MIRASOL; TROPiCS-02 and TROPION-Lung01) were included. When patients are dichotomized into younger (N=2796) and older (N=1858) groups with an age cut-off of 65 years, ADCs improved OS in both younger (HR, 0.64; 95% CI, 0.52-0.80) and older (HR, 0.56; 95% CI, 0.44-0.71) groups. An improvement in PFS was observed in younger (HR, 0.55; 95% CI, 0.46-0.66) and older (HR, 0.52; 95% CI, 0.41-0.67) patients. Subgroup analyses according to ADCs and tumor type showed a consistent survival benefit in both younger and older groups. Conclusions: A benefit in OS with ADCs was significant in both younger and older patients with a cut-off age of 65 years. Prospective real life cohort study would be of interest to confirm those results with a description of geriatric parameters to better define the population.
Advancing cancer MRD monitoring through tumor whole-genome informed, duplex ctDNA sequencing.
Authors: Lee Won-Chul , Shin Jong-Yeon , Kim Chang Woo , Kwon Minsuk , Lee Sangmoon , Connolly-Strong Erin , Oh Brian Baek-Lok , Ju Young Seok 
Published: June 2024

e15044 Background: Circulating tumor DNA (ctDNA), a cell-free DNA (cfDNA) present in the plasma of cancer patients, originates from cancer cells and serves as a crucial biomarker during cancer treatment. Despite its importance, the current limit of detection (LoD) of conventional ctDNA assays is suboptimal (0.01%; 10-4) for detecting ctDNA from microscopic residual and recurrent cancer tissues. To address this, we integrated two cutting-edge techniques: whole-genome sequencing (WGS) of primary cancer tissue (a mutation capture step) and duplex DNA sequencing-based cfDNA sequencing (mutation recapture steps). Methods: Thirteen colorectal cancer patients participated in this study. Primary tumor tissues and matched normal blood tissues were collected for WGS in the mutation capture step, while plasma samples for cfDNA sequencing in the mutation recapture steps were obtained just prior to colorectal cancer surgery and 1-month post-surgery follow-up. Tumor DNA and germline DNA were analyzed using CancerVision, a CLIA-certified clinical-grade cancer WGS platform, in the mutation capture step. In the mutation recapture steps, somatically acquired mutations from the previous step were tracked in cfDNA samples using the Concatenating Original Duplex for Error Correction (CODEC) technique, a duplex DNA sequencing technique that examines both Watson and Crick strands of double-stranded DNA molecules to discern true mutations from sequencing noise. Results: The median WGS depth of tumor and germline tissues was 40x and 20x, respectively. The mean depth of cfDNA WGS with CODEC was 25x, with a median duplex sequencing rate of 70%. Overall, 4,828-301,434 somatic base substitutions (SBSs) per sample were discovered in the capture step. Four of the thirteen tumors exhibited hypermutator characteristics with microsatellite instability features. The CODEC technique demonstrated excellent capability in tracing cancer-specific mutations in cfDNA sequencing with a technical sequencing error rate of 4 x 10-7, defining the maximum technical LoD, which is 250-fold lower errors than conventional sequencing. In our sample cohort, tumor fractions in cfDNA sequencing were robustly estimated from 0.001% (10-5), below the LoD of conventional MRD methods. Conclusions: Our integration of tumor-WGS-informed duplex cfDNA sequencing methods significantly enhances the sensitivity of sequencing-based MRD assays, achieving a technical LoD limit of 10-7 for detecting ctDNA in cancer patients. These approaches represent a breakthrough in monitoring MRD in real-world cancer patients.
Disease monitoring using plasma-based circulating tumor DNA (ctDNA) assays in rare malignancies.
Authors: Li Shenduo , Connor Dana , Fournier Lyndsey Lane , Rao Sarika , Manochakian Rami , Lou Yanyan , Zhao Yujie 
Published: June 2024

e15046 Background: ctDNA assays can be used to assess molecular residual disease, and the value of ctDNA monitoring in disease surveillance and treatment response assessment has been demonstrated in colon, breast, lung, and bladder cancers. However, the data of ctDNA in rare cancers has been lacking. We conducted this retrospective study to investigate the potential roles of ctDNA monitoring in rare tumors in both surveillance and response evaluation. Methods: ctDNA assay results of 12 patients (pts) with rare cancers including adrenocortical carcinoma (ACC) (4 pts), salivary gland cancers (3 pts), pleural or peritoneal malignant mesothelioma (4 pts), and anaplastic thyroid cancer (ATC) (1pt) undergoing treatment or surveillance in 2023 at Mayo Clinic Florida were analyzed. The trends of ctDNA levels were correlated with radiographic images findings. Results: Among the 12 patients, ctDNA was detected in at least one time point in 9 (75%) pts, including 1 (100%) ATC pt, 2 (66%) salivary gland pts, 3 (75%) malignant mesothelioma pts, and 3 (75%) ACC pts. Among these 9 pts, 5 pts had ctDNA collected at more than one timepoints, and the trends of ctDNA levels were consistent with image findings in all 5 pts. Among these 5 pts, one pt received definitive surgery for ACC with clearance of ctDNA after the surgery and one salivary gland cancer pt was undergoing surveillance and later developed disease progression. The other 3 pts were undergoing palliative systemic therapy and had responded to treatments. Conclusions: ctDNA was detectable in majority of the patients with rare malignancies reviewed in this study, including ACC, ATC, pleural or peritoneal malignant mesothelioma, and salivary gland cancers. Further study is warranted to investigate the role of ctDNA monitoring in surveillance and treatment response evaluation in rare malignancies.
Multi-omics study on the molecular mechanism of anlotinib in regulating tumor metabolism.
Authors: Lu Yu , Han Xuedan , Zheng Lufeng , Zhang Hongwei , Li Xiaoman 
Published: June 2024

e15121 Background: Anlotinib, an orally administered small molecule inhibitor of receptor tyrosine kinases (RTKs), exerts significant anti-angiogenic and vascular normalization effects. However, the mechanisms underlying its involvement in tumor metabolic reprogramming are still unclear. This study aims to investigate the distribution and expression levels of metabolites within tumors after anlotinib treatment using spatial metabolomics analysis. Methods: This study involves spatially analyzing the distribution differences of metabolites post-anlotinib administration and integrating transcriptomics and proteomics to explore the internal mechanisms of anlotinib action at a molecular level. Results: By integrating the transcriptomics and proteomics analyses, we identified that anlotinib treatment primarily modulated four metabolic pathways, including taurine and hypotaurine metabolism, steroid synthesis, pentose phosphate pathway, and lipid biosynthesis. This regulation significantly influenced the metabolic levels of compounds such as sulfonic acids, cholesterol, inositol phosphate pyrophosphate, and palmitoyl-CoA in the tumor, thereby impacting tumor initiation and progression. Conclusions: This study provides potential metabolic biomarkers for anlotinib treatment in tumors, and may identify potential biomarkers and pathways associated with the therapeutic efficacy of anlotinib treatment.
Concurrent hyperthermic intraperitoneal chemotherapy and intraoperative radiotherapy with cytoreductive surgery in patients with rectal cancer with peritoneal carcinomatosis.
Authors: Arabi Tarek , Alaswad Marwan , Sabbah Belal Nedal , Al Otry Abdullah , Hejazi Alwalid , Ismail Aya , Jaamour Heba , Alhosainy Ziad , Al Homoud Samar , Azzam Ayman , Amin Tarek 
Published: June 2024

e15571 Background: Rectal cancer (RC) is often associated with peritoneal carcinomatosis (PC). Hyperthermic intraperitoneal chemotherapy (HIPEC) and intraoperative radiotherapy (IORT) have been shows to reduce recurrence and effectively treat PC across several cancers. However, little evidence is available regarding the concurrent use of HIPEC and IORT alongside cytoreductive surgery (CRS) in the literature. Methods: We retrospectively reviewed the medical records of RC patients with PC who received HIPEC plus IORT during CRS at the King Faisal Specialist Hospital and Research Centre. Demographic data, PC index (PCI), completeness of cytoreduction (CC), and tumor staging were collected. Overall survival (OS) was calculated from the time of surgery until death or last follow-up. Recurrence-free survival (RFS) was calculated from the time of surgery until recurrence or last follow-up. Unadjusted hazard ratios (HR) were used to determine the impact of parameters on OS or RFS. Results: 17 patients were included in our analysis. Basic demographic data can be found in Table 1. The most common operation performed was rectosigmoid resection in 7 (41.2%) patients, followed by low anterior resection in 6 (35.3%). The pT stage was T0 in 1 (5.9%), T4a in 7 (41.2%), and T4b in 9 (52.9%). The pN stage was N0 in 11 (64.7%), N1a in 1 (5.9%), N1b in 2 (11.8%), N1c in 2 (11.8%), and N2b in 1 (5.9%). There was positive resection margin in 2 patients. The PCI was ≤6 in 15 (88.2%), and the CC score was 0-1 in all patients. No patients had intraoperative complications. 12 (70.6%) received mitomycin C, 4 (23.5%) received cisplatin and mitomycin C, and one patient received a reduced dose of mitomycin C due to old age. 2 (11.8%) patients received two doses of IORT. 11 (64.7%) patients had postoperative complications, of which all were Clavein-Dindo grades 1-3b. Recurrence occurred in 11 (64.7%). The median OS was not reached, and the median RFS was 12 months. There were no parameters associated with OS. Male gender (HR: 7.7, 95% CI: 1.4-57.3), pM1 (HR: 4.5, 95% CI; 1.2-18.1), and perineural invasion (HR: 6.5, 95% CI: 1.2-49.3) were associated with poor RFS in univariate analysis. Conclusions: Incorporating HIPEC and IORT into CRS may be an effective treatment strategy for RC patients. Presence of distant metastasis and perineural invasion can be predictors of rapid recurrence. [Table: see text]
Systemic assessment of manual circular stapler versus powered circular stapler for anastomosis in rectal cancer: A multicenter prospective cohort study.
Authors: Li Xinxiang , Chen Yikuan , Zhang Ruijia , Luo Dakui , Liu Fangqi 
Published: June 2024

e15614 Background: Mechanical anastomosis offers several advantages over traditional hand-sutured anastomosis. However, complications such as anastomotic leaks, strictures, and bleeding persist due to factors like interactions between staples and tissue. Powered circular anastomosis is an effective method to address these issues. Currently, there are no domestic studies on the application of powered-anastomosis technology in colorectal anastomosis. Methods: The study adopted a multicenter, randomized, parallel-controlled, non-inferiority study design, with a 1:1 random allocation ratio. The study involved 187 patients with rectal cancer who underwent Dixon surgery using IntoCare™ disposable powered circular stapler (ICS), and 195 patients who received similar process with manual circular stapler (MCS). The efficacy of stapler was evaluated by anastomosis success rate, anastomosis-related adverse events, anastomosis device performance assessment, operation time, anastomosis time, and postoperative recovery. Safety evaluation indicators included adverse events, vital signs, and laboratory tests. Results: Baseline demographic characteristics showed no notable disparities between two groups (Table 1). A high proportion of patients, 99.47% in the MCS group and 99.49% in the ICS group, successfully completed anastomosis. In the MCS group, the average anastomosis duration was clocked at 2.84 minutes (min) (±2.3), with a median time of 2.0 min (ranging from 1.0 to 22.0 min). In contrast, the ICS group exhibited a slightly quicker average anastomosis duration of 2.40 min (±1.7), and a comparable median time of 2.0 min (but with a narrower range from 1.0 to 15.0 min). Adverse events did not differ significantly between two groups. Conclusions: The results uncovered the powered stapler could considerably reduce stapling time while maintaining a safety profile. Notably, the incidence of patients with anastomotic leakage one month post-surgery, and anastomotic stricture six months post-surgery in the powered stapler group, was lower than those in the manual stapler group. This suggests that the anastomosis created by the powered stapler is more stable and promotes more effective postoperative anastomotic healing. Clinical trial information: NCT05879172 . [Table: see text]
Prevalence and predictors of coronary artery stent re-stenosis in patients with cancer with prior history of percutaneous coronary intervention: A nationwide analysis.
Authors: Aryal Badri , Sueldo Alexandra , Turk Ekrem , Quevedo Andres 
Published: June 2024

e24018 Background: Data regarding the prevalence, and predictors of development of in-stent restenosis (ISR) in cancer patients undergoing percutaneous coronary intervention (PCI) are scarce. This study aimed to identify factors associated with the development of ISR following PCI in cancer patients. Methods: This is a retrospective cohort study using the National Inpatient Sample(NIS) from 2016 to 2020. Discharges with ICD-10 CM code indicating stenosis of coronary artery stent, and secondary ICD-10 CM code indicating cancer, and prior history of PCI were included. Primary outcome was development of ISR. Multivariate logistic regression model was used to identify predictors of ISR development, and p value of less than 0.05 was considered significant. Results: There were 873,320 patients who met inclusion criteria, among which 4060 patients were admitted for coronary stent re-stenosis. Mean age of included patients was 73, and 31% were females. The prevalence rate of in-stent restenosis was 0.46%. Factors associated with increased odds of development of ISR included diabetes (OR 1.31, 95% CI 1.13-1.51, p < 0.001), dyslipidemia (OR 1.92, 95% CI 1.60-2.31, p < 0.001), congestive heart failure (OR 1.78, 95% CI 1.52-2.06, p < 0.01), carotid disease (OR 1.99, 95% CI 1.43-2.78, p < 0.001), and aortic disease (OR 1.83, 95% CI 1.12-2.98, p 0.01). Age, gender, race, median household income, hospital location and hospital teaching status didn’t exhibit statistically significant increased risk. Conclusions: The prevalence of in-stent restenosis was 0.46%. Appropriate management of risk factors such as diabetes, dyslipidaemia, congestive heart failure is prudent to prevent development of ISR in cancer patients, underscoring the importance of regular cardiology follow up, along with routine cancer care.
Effect of fructose on anthracycline and HER-2 blocking agent mediated cardiotoxicity through NLRP3 and MyD88 mediated pathways: New roles of sweeteners in cardio-oncology.
Authors: Paccone Andrea , Quagliariello Vincenzo , D'Aiuto Giuseppe , Iovine Martina , Giacobbe Ilaria , Arianna Raffaele , Izzo Francesca , Maurea Fabrizio , Barbato Matteo , Inno Alessandro , Giordano Vienna , Maurea Nicola 
Published: June 2024

e24020 Background: Combinatorial therapy based on anthracyclines and HER-2 blocking agents increases the risk of cardiomyopathy in women with breast cancer. Fructose is a monosaccharide associated with high risk of diabetes, non-alcoholic fatty liver disease, atherosclerosis and visceral obesity. A high fructose diet is a potential cardiometabolic risk factor and may increase cardiac risk in women with breast cancer treated with cardiotoxic drugs. In this study, we highlighted the role of sweeteners fructose in the worsening of cardiotoxicity induced by combinatorial therapy anthracycline-HER2-blocking agents. Methods: Human cardiomyocytes were pre-exposed with doxorubicin combined to trastuzumab (at 300 and 1000 nM) for 48 and 72h alone or combined to fructose at 0.25, 1 and 2.5 mM. After the incubation period, we performed the following tests: determination of cell viability, through mitochondrial dehydrogenase activity, study of lipid peroxidation (quantifying cellular Malondialdehyde and 4-hydroxynonenal), intracellular Ca2+ homeostasis. Moreover, pro-inflammatory studied were also performed (activation of NLRP3 inflammasome; expression of peroxisome proliferator-activated receptor-α; transcriptional activation of p65/NF-κB and secretion of cytokines involved in cardiotoxicity (Interleukins 1β, 8, 6, CXCL-12). Results: High fructose increases significantly cell mortality of cardiomyocytes exposed to doxorubicin and trastuzumab through the activation of NLRP-3 and Myd-88 expression. Intracellular Ca++ levels were also increased of 4 times compared to non-fructose exposed cardiomyocytes; MDA and 4-HNA levels were increased of 48,3 and 51,2 % compared to non-fructose exposed cells (p<0.001). Fructose increases IL-1, IL-6 and CXCL-12 expression in cardiomyocytes in a concentration dependent manner, compared to doxorubicin-trastuzumab group (p<0.05). Conclusions: Data of the present study indicate that fructose induces a pro-inflammatory phenotype in human cardiac cells exposed to anticancer cardiotoxic drugs, providing even more data on the harmful role of fructose as a key player of cardiotoxic phenomena.