bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of next-generation genomic sequencing (NGS) applied to cerebrospinal fluid (CSF) in the identification of actionable mutations in Mexican patients.
Authors: González Espinoza Iván Romarico , Sánchez-Sosa Sergio , Castro-Ponce Abraham , Sandoval-Amaro Gabriela , Juárez-Salazar Gabriela , Nieva Ana Isabel , Íñiguez López Galo Ismael , Acosta Ponce de León Eric , Aranda Jorge Esteban , Garibay Diaz Julio Cesar , Chiquillo-Domínguez Mariana 
Published: July 2024

e14000 Background: Among the benefits offered by NGS from liquid biopsy are the molecular classification of neoplasms as well as the identification of therapeutic targets, without the need to obtain a biopsy of the tumor when it is not feasible. Since 2016, the World Health Organization has included these biomarkers as part of its classification for better management. Additionally, in the case of metastatic tumors, it allows the identification of therapeutic targets as well as resistance mutations and even driver mutations to better understand their biology. In this study, we evaluated the efficacy of CSF NGS in the identification of actionable mutations in patients with CNS neoplasms, and its potential impact on the personalization of cancer treatments for patients in our center. Methods: A retrospective analysis of nine cases was performed in which CSF was used to identify NGS-actionable mutations, collecting, and descriptively analyzing clinical and molecular data from these patients. Results: Mean age was 51.89 years; 55.56% were men and 44.44% women; 66.67% had family history of cancer, of which 83.33% were first-degree relatives; 88.89% had neurological symptoms prior to the study; 33.33% were primary CNS tumors; 55.56% were secondary tumors metastatic to the CNS; 11.11% were indicated due to suspected CNS metastasis. At least 1 genomic alteration was found in 89% of the cases; the most frequently altered gene in primary tumors was TP53 (66.67%). In secondary tumors, the most frequently altered genes were AR and EGFR with 40% incidence each; Approved therapies were found in 55.56% of the cases, therapies approved in other neoplasms in 44.44%, and phase 2 or 3 clinical trials were available in 88.89%. Specific alterations found in are listed in the table. Survival rate at 6-month follow-up was 55.56%. Conclusions: In our patients, the study of CSF through NGS effectively identified actionable mutations with approved treatment in the analyzed neoplasms, other neoplasms, or clinical trials available for enrollment in most cases. In one case, it was possible to rule out the presence of metastasis in CNS, avoiding unnecessary toxicity. To our knowledge, this is the first study in our country that reports the findings of this technique in medical practice, however, more research is needed in bigger populations to optimize and validate the implementation of this study as part of the approach to patients with CNS tumors. [Table: see text]
Descriptive analysis of brain metastases (BM) of solid neoplasms in an academic hospital from a low- and middle-income country (LMIC) with a Hispanic population.
Authors: Dominguez-Porras Victor Antonio , De La Pena Lopez Ildefonso Roberto Roberto , Flores-Balcázar Christian Haydeé 
Published: July 2024

e14015 Background: Multidisciplinary management of BM of solid cancers integrates different combinations of treatment modalities. The scarcity of SRS centers has prevented widespread adoption of this therapy for appropriately selected patients. Methods: One-hundred eighteen (51.7% female, 48.3% male, median age 59 years) BM patients from a National Health Institute from Mexico (INCMNSZ) were included and analyzed. Results: The most common primary tumors were lung and breast cancers (25 cases each, representing 21% of the whole cohort), kidney cancer (14%), male germ cell tumors (10%), metastatic carcinoma of unknown primary (CUP) (5%), upper- and lower- gastrointestinal cancers (5%), thyroid differentiated cancers (5%), followed by melanoma, prostate, ovarian, hepatobiliary cancers and sarcoma (3% each of them) and urothelial carcinoma (2%) being the least common. No biopsy was reported for only one case. The most common histomolecular tumors were adenocarcinoma of the lung (17 cases), renal cell carcinoma (17), triple negative (TN) breast cancer (BC) (9), HER-2+ BC (7), Nonseminomatous germ cell tumor (7), CUP (6), ER+/HER-2+ BC (5), Germ cell tumor with choriocarcinoma (5), small-cell lung cancer (SCLC) (5), melanoma (5), prostate adenocarcinoma (5), thyroid differentiated cancer not otherwise specified (NOS) (5). Rectal adenocarcinoma, high-grade serous ovarian cancer, ER+/PR+ BC, sarcomas and NSCLC (3 cases, each) and urothelial carcinoma (2). Rare tumor subtypes, with one case, each included hepatocellular carcinoma, PR+/HER2+ BC, follicular thyroid cancer, esophageal, gastric and colonic adenocarcinomas, neuroendocrine prostate, neuroendocrine gallbladder, endometrial, large cell neuroendocrine lung carcinomas and cholangiocarcinoma. A solitary BM was present in 44 patients (37.3%), 2-3 BM in 30 (25.4%) and >3 BM in 44 patients (37.3%). 18 patients (15.2%) were not symptomatic at the time of diagnosis. 79 patients were treated with Whole-Brain Radiotherapy (WBRT), ten with a combination of surgery and adjuvant WBRT, seven with surgical resection without radiotherapy, only five included SRS as part of their treatment and seventeen received only supportive care. There was no difference in overall survival (OS) between treatment modalities excluding supportive care (p=0.05). Conclusions: Our experience from a LMIC with Hispanic population highlights that more than 50% of BM metastasize from solid tumors different from lung and breast cancers. Even though SRS has been included in recent guidelines from ASCO and ESMO, WBRT is the option most commonly included in multimodality treatments.
Immunological profiling of glioblastoma cellular composition to predict response to dendritic cell vaccination.
Authors: Lepski Guilherme , Peres Nataly , Santos Patricia Bergami , Pinho Mariana , Chauca-Torres Nadia , Evangelista Gabriela Coeli , Teixeira Sarah , Flatow Elizabeth , de Oliveira Jaqueline Vaz , Fogolin Carla , Arévalo Analía Leonora , Alves Venâncio A , Barbuto Alexandre 
Published: July 2024

e14037 Background: Glioblastomas are the most common primary malignant brain tumors, comprising 2% of all adult cancers. Despite recent advancements in genetic classification and targeted therapies for specific mutations, there has been no significant improvement in overall life expectancy for the majority of patients. Last year, our research group reported promising results from a phase II prospective trial involving allogeneic dendritic cell vaccination. To date, six out of 37 reported cases remain alive without tumor recurrence, exhibiting a performance status of 90 to 100% according to the Karnofsky Performance Scale (KPS) three years after the initiation of vaccination. Methods: In this study, we focused on the immune cell infiltration observed at the time of tumor excision in enrolled patients. We utilized flow cytometry to quantify cells expressing membrane CD86, CD45, HLA-DR, PD-L1, CD11b, and CD14, in addition to assessing IDH-1 status, age, gender, KPS, gender, ECOG, symptomatology, and the number of vaccines administered during the trial. Our goal was to predict responsiveness in terms of overall survival using a neural network prediction algorithm with three hidden nodes and five seeds for improved reproducibility. We employed the random holdback method for algorithm validation. Results: From the 37 enrolled patients, we successfully obtained viable tumor cells from 19 frozen samples. The model achieved an RSquare value of 0.71 after training and 0.66 after validation (where 1 indicates a perfect model and 0 implies no improvement over a constant model). Similar RSquare values in both training and validation sets indicate strong predictive power. Positive predictors of overall survival included HLA-DR positivity, PD-L1 positivity, IDH-1 mutation status, the presence of focal deficits, and higher KPS scores, while negative predictors were CD86 expression, older age, symptoms of intracranial hypertension (ICH), and higher ECOG performance status. Conclusions: In conclusion, the neural network algorithm described herein enables the prediction of responsiveness to dendritic cell vaccination in terms of overall survival, based on clinical features and the profile of immune cell infiltration observed at the time of tumor excision.
Prevalence and outcomes of acute kidney injury among hospitalized patients with gastric cancer: Insights from a National Inpatient Sample study (2018-2020).
Authors: Iqbal Rabia , Gaddam Mrunanjali , Bajwa Ahmad Taimoor , Jayakumar Jayalekshmi , Ginjupalli Manasa , Kumar Vikash , Nanavaty Dhairya , Colon Ramos Ana , Clement Jincy 
Published: July 2024

e16124 Background: Acute kidney injury (AKI) occurs in 50-60% of the patients admitted to the hospitals, and up to almost 20% of those patients have underlying cancer. AKI has been associated with high mortality and adverse outcomes in cancer patients. This relationship between cancer and kidney health, known as "the kidney-cancer connection has attracted considerable interest in research circles. In this study, we aimed to evaluate the outcome of AKI in hospitalized patients with gastric cancer. Methods: A retrospective analysis was conducted using the National Inpatient Sample database from 2018 to 2020 and the ICD- 10 codes to identify the patients > 18 years old with the principal diagnosis of Gastric Cancer. We evaluated the effect of acute kidney injury (AKI) on mortality, morbidity outcomes, and resource usage in patients with gastric cancer. Categorical variables underwent comparison using the chi-square test, while continuous variables were compared using the t-test. Multivariate analysis was conducted to derive the odds ratio, and all weighted analyses were carried out using STATA. Results: We identified a total of 123,935 patients with a primary diagnosis of gastric cancer who were hospitalized between 2018 and 2020 in the United States. Out of them, 20% (24,787) of the patients had developed acute kidney injury during the hospital admission. The mean age of the patients was 69 years. Of these patients, 67% were male, and the remaining 33% were female. The mortality for gastric cancer patients with AKI was 18.3%, while it was 4.7% for patients without AKI. After adjusting for confounders, AKI had higher odds of mortality (Adjusted odds ratio [aOR] for mortality 4.41, 95% confidence interval [CI]: 3.96-4.91, P < 0.001). AKI was also associated with higher resource utilization, including a higher length of stay (LOS) (mean LOS increased by 9.5 days vs 6.5 days in patients without AKI) and higher hospital charges (by $127,814). Conclusions: Our study concludes that the patients with gastric cancer who developed Acute Kidney Injury during the hospital stay had worse outcomes. Identifying AKI early on can help with timely intervention, which can reduce adverse outcomes. Thus it is extremely important for nephrologists and oncologists to closely monitor patients' renal function throughout their treatment.[Table: see text]
Discovering urinary protein biomarkers for hepatocellular carcinoma in the population of patients with chronic hepatitis B: A single-center case-control study.
Authors: Zhang Yuke , Huang Yongfa , Xing Jiali , Wang Yuxin , Jin Bao , Xue Runze , Guo Ye , Chang Xiaoyan , Guan Mei , Liu Xiao , Wan Xueshuai , Zhao Hong , Hong Zhixian , Xu Haifeng , Wu Jianqiang , Mao Yilei , Du Shunda 
Published: July 2024

e16230 Background: Chronic hepatitis B (CHB) can result in hepatocellular carcinoma (HCC) imposing a substantial health and economic burden worldwide. Early detection of hepatitis B virus-related HCC (HBV-HCC) in CHB with potential biomarkers has emerged as an urgent and challenging task. Recent progression of urinary proteomics provides a promising method for HBV-HCC biomarker discovery. Methods: This single-center case-control study, conducted at Peking Union Medical College Hospital, enrolled 33 patients with HBV-HCC, 26 patients with CHB, 30 healthy controls, and 33 controls with other types of cancer. Urine proteomes were analyzed using liquid chromatography with tandem mass spectrometry by data-dependent acquisition or parallel reaction monitoring, respectively. Differential analysis was carried out with limma package in R software, and the origin of selected proteins was confirmed with immunohistochemistry of surgical specimens. The diagnostic performance of the biomarker panel was evaluated with area under receiver operator curves (AUROC). Results: 21 urinary proteins were significantly upregulated in HBV-HCC compared with CHB samples, playing key roles in vesicular transportation, cytoskeleton-extracellular matrix interaction, and tumor development according to enrichment analysis. Immunohistochemistry validated the differential expression of 4 urinary proteins (4UP: HNRNPM, ADGRG1, APOC1, and RALA) across cancerous and adjacent normal liver tissues. These proteins were specifically found in HBV-HCC but not in CHB, healthy control, or other cancer controls. The AUROCs of 4UP individually (0.642 for APOC1, 0.780 for HNRNPM, 0.755 for ADGRG1, 0.729 for RALA) were no worse than that of serum α-fetoprotein (AUROC = 0.751), and the 4UP panel unified via logistic regression showed an AUROC of 0.828. Conclusions: Urinary proteomics revealed HNRNPM, ADGRG1, APOC1, and RALA as biomarkers to distinguish HBV-HCC from CHB. The 4UP could be traced back to HBV-HCC tumor cells, shedding light on pathogenesis of HBV-HCC. [Table: see text]
An analysis of the evidence underpinning the surgical treatment of hepatocellular carcinoma.
Authors: Radi Imad , Zhan-Moodie Samantha , Scanlan Luke , Sapkalova Viktoriya , Resheek Nerella , Mehra Mehul , Colquhoun Steven , Yakoub Danny 
Published: July 2024

e16278 Background: The American Association for the Study of Liver Diseases (AASLD) and National Comprehensive Cancer Network (NCCN) guidelines on Hepatocellular Carcinoma (HCC) surgery are based on evidence from many different systematic reviews (SRs) and meta-analyses (MAs). Quality of these studies needs to be standardized. Methods: SRs and MAs cited in AASLD and NCCN HCC (2023) surgery guidelines were collated by two independent reviewers. An independent third reviewer acted as tie-breaker when necessary. The standardized assessment tools, the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Assessing the Methodological Quality of Systematic Reviews (AMSTAR) were used to evaluate the quality of these studies. Quality of studies was determined based on adherence to items of the checklist. The PRISMA and AMSTAR checklists consist of 41 and 16 items, respectively. Results: Overall, 13 studies were identified, 9 from AASLD guidelines and 4 from the NCCN. Studies were published between 2007 and 2023, with 38% being published in the last 5 years. Studies had an average of 23,829 patients. Many of the studies (71%) reported use of the PRISMA checklist, but no studies cited the AMSTAR checklist. Studies had an average adherence of 68% to the PRISMA checklist, with a median of 76% (range 17-88%). 23% of studies adhered to less than half of the PRISMA checklist. Looking at the AMSTAR checklist, studies had an average adherence of 51%, with a median of 56% (range 4-72%). 31% of studies adhered to less than half the AMSTAR checklist. Adherence was lowest in items involving availability and accessibility of protocols, assessing risk of bias, and transparency of protocols. Additionally, no papers reported funding sources of their reviewed articles. Conclusions: There is significant room for improvement in MAs and SRs about HCC surgical management. Many quoted studies needed more rigorous methodology and quality control for conducting and reporting. It is important to fully investigate and communicate the biases present in MAs and SRs to readers. PRISMA and AMSTAR checklists can be used when reviewing and selecting evidence for future guideline development to offer the most complete and transparent understanding of data presented.
Influence on surgical approach in hepatocholangiocarcinoma: A demographic and socioeconomic analysis.
Authors: Al Kurnas Mohammed , Becker Ashley , Wu Xinxin , Silberstein Peter T. 
Published: July 2024

e16280 Background: Hepatocholangiocarcinoma (HCC-CC) is a rare and aggressive malignancy of the liver that contains histopathological features of both hepatocellular carcinoma and cholangiocarcinoma. Surgery is the mainstay of treatment, and the surgical approaches used include radical hepatic resection, laparoscopic, and robotic surgery. There has yet to be a study that explores the impact of demographic features on the choice of surgical modality in patients with HCC-CC. The National Cancer Database (NCDB) was analyzed to determine the effects of demographic features on surgical modality and overall survival. Methods: A retrospective cohort analysis utilizing the NCDB included 2,449 patients diagnosed with HCC-CC (ICD-8180/3) between 2004-2020. Surgical modality was categorized into either open or minimally invasive by the preliminary treatment. Minimally invasive techniques included robotic-assisted and minimally invasive. Race, sex, age at diagnosis, income level, insurance used, distance from the facility, and the status of the facility as an academic center on the surgical modality were compared using Pearson Chi-squared tests or independent samples t-test as pertinent. Multivariate analysis with binary logistic regression was used to analyze the following categorical variables in relation to choice of surgical modality: race, sex, income, insurance, sex, and facility type. Surgical treatment modality on overall survival was analyzed by the Kaplan-Meier method. Exclusion criteria included missing data. Results: Most cases analyzed were White (75.8%), male (67.5%), and had government insurance as the primary payor at diagnosis (60.6%). Of the cases analyzed, 625 underwent surgery (25.5%). Patients who underwent minimally invasive surgery were more likely to be government-insured than patients who underwent open surgery (69.8% vs. 55.6%, P < 0.05). Patients who underwent open surgery were younger on average (61.4 vs. 66.0 years, P < 0.05). There was no significant difference in distance from residence to the treatment facility between the two surgical approaches. Multivariate analysis showed that patients treated at academic centers were less likely to receive minimally invasive surgery (28.1%) over open surgery (71.9%; P = 0.041, 95% CI 0.469-0.985) without statistical significance for race, sex, income, or insurance. The average survival time was significantly longer in open vs minimally invasive surgery (67.9 vs. 55.3 months, P < 0.05). Conclusions: We identified that patients who underwent open surgery had significantly better overall survival with an average difference of 12.6 months. Even after accounting for other factors, the choice of surgical modality was significantly influenced by treatment at an academic institution. Patients receiving care at an academic facility are more likely to receive open surgery leading to overall increased survival.
Quality of life (QoL) benefits following 177Lu-DOTATATE therapy in patients (pts) with 68Ga-DOTATATE PET positive primary site agnostic neuroendocrine tumors (NET).
Authors: Wong Rebecca KS , Myrehaug Sten , Juergens Rosalyn A. , Laidley David , Ezzat Shereen , Beauregard Jean-Mathieu , Levine Oren Hannun , Veit-Haibach Patrick , Metser Ur , Driscoll Brandon , Shessel Andrea , Yeung Ivan , Mesci Aruz , Publicover Julia , Sun Edward , Lajkosz Katherine 
Published: July 2024

e16291 Background: The QoL experience during the 1st year of follow up for 68Ga-DOTATATE PET positive primary site agnostic pts with progressive metastatic NET enrolled in a prospective single arm clinical trial of 177Lu-DOTATATE therapy (OZM 067) is described here. Methods: Pts with progressive NET, Ki67 Index < 30%, adequate organ function & ECOG £2 were eligible. Only pts demonstrating positive disease (Krenning score 3-4) on 68Ga-DOTATATE PET were eligible to proceed to 177Lu-DOTATATE therapy (4 cycles at 8- to 12- week intervals. Primary outcome was progression free survival (PFS) at 12 mths. QoL (EORTC QLQ 30 and GINET21) at baseline, 6, 12, 18, 24, 30 months were recorded. Summary scores at time point of interest, and their change from baseline were estimated using a mixed model repeated measure, with baseline assessment included in the model as covariate. Data were normalized with a range of 0-100. A positive change score for Global Summary Status, Functioning Domains, and a negative change score for Symptom Scales and Items represent improvement. A ≥5 point change score is used as a threshold for Minimal Clinically Important Difference (MCID). Results: 195 pts were enrolled. 13 pts were 68Ga-DOTATATE PET negative while 5 pts withdrew consent. 177 pts received at least one dose of 177Lu-DOTATATE. All pts enrolled were eligible for a minimum of 12 mths follow up at time of data lock. The primary site was GEPNET in 143 (81%) and non GEPNET in 34 (19%). At 12 mths, the median follow-up was 33 (range 3-71) mths. PFS and OS were 81 (95% CI: 75-86)% and 92 (87-95)% respectively. QoL data at the following timepoints baseline, 6 & 12 (±2) mths were available in 174,128 & 111 pts respectively. The top three symptoms captured in EORTC QLQ 30 was Fatigue (32.5 SD 23.8) , Insomnia (26.7 SD 28.1) and Diarrhea (22.1 SD 29.4). At 12 mths, an improvement in mean score of ≥MCID in Global Health status (GHS) (+5.4), Role Fc Scale (+7,1), Social Fc Scale (+8.7) and multiple symptoms (Fatigue, Pain, Appetite, Constipation, Diarrhea, Financial Difficulties), Sexual fc, Social, Body image (Table 1) were captured. Conclusions: Patients with primary site agnostic 68Ga-DOTATATE PET positive NET experienced improvement in multiple quality of life domains including multiple symptoms post 177Lu-DOTATATE at 12 mths. Sexual fc and body image had the largest improvement. Clinical trial information: NCT02743741 . [Table: see text]