bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcomes in patients with early-stage breast cancer in a racially and ethnically diverse patient population.
Authors: Shin Denny Donggun , Switchenko Jeffrey M. , Marra Angelo , Kalinsky Kevin 
Published: July 2024

e12532 Background: Despite the growing evidence that substantial disparities exist in breast cancer care per socioeconomic status, the racial and ethnic disparities that contribute to clinical outcomes in patients with early breast cancer are not well understood. This analysis attempts to better characterize these differences in a diverse group of patients with early breast cancer. Methods: Patients were identified from an institutional database from the Winship Cancer Institute, which included those with pathologic stage I-III breast cancer with varying hormone receptors (HR) and HER2 receptor status who received care between 1999-2023. Patients with ductal carcinoma in-situ (DCIS) and with metastatic breast cancer at diagnosis were excluded from this retrospective analysis. Using variables such as race, treatment received, pathological stage, tumor grade, and histology, we performed univariate and multivariate analysis for IDFS, defined as pts who are alive and free of any breast or other cancer. Results: 449 patients were included, which comprised of 148 non-Hispanic African American (33%) and 301 (66%) Caucasian women. Mean age at diagnosis was 60; 77.3% of patients were post-menopausal, and 79.1% received operable endocrine therapy. 76.4% of patients had invasive ductal carcinoma (IDC) and 13.1% invasive lobular carcinoma (ILC). Only 9.8% received chemotherapy. In univariate analysis, patients who were triple negative (n=30, 6.8%) had worse IDFS compared to those who were HR+/HER2- (n=351) (Hazard Ratio=2.49, p=0.036) Additional patients with larger tumors with pT2-pT4 (n=133, 30.4%) had worse IDFS compared to those with pT0-pT1 (p=297, 67.8%) tumors (HR=2.04, p=0.014). There were no significant differences in clinical outcomes by patient race or by lymph node involvement. Conclusions: In our lower-risk, racially diverse cohort, our findings demonstrate that patients with HR-/HER2- breast cancer and larger tumors have worse IDFS. More analyses should be performed on a population with higher-risk patients and larger cohort. Future studies should continue to focus on early screening, as well as novel therapeutics to treat HR-/HER2- disease.
Characterizing vaginal stenosis in female cancer survivors.
Authors: Mihulka Olivia , Curran Melissa , Wolde Tizeta M. , Moore Jessica Firdman , Rojas Kristin E. 
Published: July 2024

e13800 Background: Vaginal stenosis is an underreported and undertreated sequelae of cancer treatment that leads to pain with sexual activity and inability to tolerate pelvic exams. We sought to describe a population of female cancer survivors presenting with sexual health concerns and identify factors associated with presence of vaginal stenosis on genitourinary exam (GU). Methods: A retrospective analysis included 134 female cancer survivors presenting to a sexual health after cancer program in South Florida (2020-2023). Sexual function and GU anatomy disruptions were evaluated using the Female Sexual Function Index (FSFI) and Adapted Vulvovaginal Exam Score (AVES), respectively. Vaginal stenosis was defined as presence of vaginal agglutination, shortening, or scarring/adhesions on GU exam. Patients who did and did not present with vaginal stenosis were compared using Chi-squared analysis, while independent t-test analyzed FSFI and AVES scores. Results: Of 134 patients, 116 met criteria for inclusion and underwent a GU examination. Median age was 45 (23-75). Race, ethnicity, menopausal status, cancer type, and treatment type were similar between groups. The rate of vaginal stenosis in patients with breast cancer was 13.4%, gynecologic cancer was 27.2%, and 28.6% with other cancer types (including gastrointestinal, hematologic, sarcoma). Higher median AVES scores, which denote more severe GU exam disruptions, were found in patients with vaginal stenosis compared to those without (13 vs 5; p<.001). While overall FSFI scores were similar between groups, median FSFI pain domain scores were lower in those with vaginal stenosis compared to those without stenosis (7.8 vs 11; p=0.037). Conclusions: Factors associated with the development of vaginal stenosis in female cancer survivors are not well-described. Our analysis reveals that vaginal stenosis develops in women treated for a variety of cancer types across the age continuum. Identifying and treating this severe sequela of treatment is a critical step in improving the sexual health of female cancer survivors. Ongoing work seeks to evaluate the safety and efficacy of treatments to reverse GU exam disruptions after cancer treatment. [Table: see text]
Transcriptional mechanisms of phenotypic plasticity in glioblastoma.
Authors: Mukherjee Ishita , Park James H. , Patel Anoop P. , Baliga Nitin S. 
Published: July 2024

e14027 Background: Primary glioblastoma (GBM) tumor cells exhibit plasticity and can adopt different cellular states that exhibit dynamic transitions between states. This could be one of the mechanisms for treatment escape and leads to poor prognosis in GBM. In this regard, we sought to uncover transcriptional regulatory mechanisms responsible for this phenotypic plasticity in GBM. Methods: Standard of care (SOC) treatment (radiation and temozolomide) modulates transcriptional regulatory networks (TRNs) of the tumor cells and drives treatment resistance. Since TRNs could be key mechanistic drivers for state transitions, integrated single-cell RNA sequencing (scRNAseq) data of primary and relapse patient samples (11) were analyzed with scMINER. Our method uses a systems biology framework to identify cell states (St_1 to St_n) in terms of regulatory networks and their activities. Clustering of co-regulated gene modules (regulons), enabled the identification of transcriptional programs and regulatory mechanisms that specify tumor cell states. Results: Activity patterns of 38 transcriptional programs clustered tumor cells from the patients into 21 states. Preliminarily, we observed common regulatory network cell states (St_1, St_2, St_5, St_6) across patient tumors. Additionally, primary tumor cells of a patient (UW14) transitioned from initial cell state(s) observed across multiple patients (e.g., St_1) to a recurrent state (e.g., St_9) through a trajectory driven by transcription factors (TFs). Herein, scMINER regulatory network inference method also defines master TFs (TFs that regulate the majority of the other TFs in the network) that were used to characterize initial (St_1) or recurrent (St_9) cell states. Moreover, certain transcription factors (22) and their co-expressed target genes (regulons) also exhibit variation in expression across the pseudotime trajectory (from St_1 to St_9) including masterTFs such as SOX9 and MECOM. Conclusions: Therefore, we observed that shared cell states may exist across patients (primary and relapse) although in different proportions. Our analysis suggests a de-differentiation trajectory from neuronal cells to developing GBM stem cells and predicts transcription factors that could be playing an important role therein. Moreover, similar transcriptional regulatory mechanisms may promote transitions between primary and recurrent tumor cell states that exhibit phenotypic plasticity.
Correlation of therapy-induced neutropenia with survival in patients with metastatic pancreatic cancer treated with GSK-3 inhibitor elraglusib (9-ING-41) in combination with gemcitabine/nab-paclitaxel in the 1801 phase 2 study.
Authors: Ugolkov Andrey , Koukol Austin , Kellinger Caroline , Smith Sheri Lynn , Gallipoli Susan , Gagnon Suzanne , Seifarth Chris , Reich Steven D. , Mazar Andrew Paul 
Published: July 2024

e16311 Background: Previously, elraglusib (9-ING-41), an inhibitor of Glycogen Synthase Kinase-3 (GSK-3), was shown to potentiate the anticancer effects of chemotherapeutic drugs in preclinical models of cancer. The combination of elraglusib and gemcitabine/nab-paclitaxel (GnP) is currently being investigated in a randomized, open-label 1801 phase 2 study as a first-line therapy for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). Chemotherapy-induced neutropenia is a common dose-limiting toxicity resulting in dose reductions and/or treatment interruptions. Present evidence shows that therapy-induced neutropenia (TIN) grade 3-4 correlates with survival and is a potential marker for improved clinical outcome in elraglusib/GnP-treated patients. Methods: We correlated overall survival (OS) and time-to-treatment discontinuation (TTD) with TIN grade 3-4 in 72 (GnP arm) and 155 (elraglusib/GnP arm) mPDAC patients previously untreated for advanced disease (1801 Part 3 Arm B study; NCT03678883). TTD was defined as the date of first dose to the date of treatment discontinuation or death. The Kaplan-Meier log-rank test was used for statistical analysis. A p-value < 0.05 was considered statistically significant. Results: The rate of grade 3-4 TIN was 22% (16/72 patients) and 47% (72/155 patients) in the GnP and elraglusib/GnP groups, respectively. Based on 28% of all recorded death events in elraglusib/GnP group and 36% in GnP group, we found that grade 3-4 TIN was significantly associated with improved OS in patients treated with elraglusib/GnP (median OS: 14.4 vs 5.9 months; P < 0.05) but not in patients treated with GnP (median OS: 7.6 vs 7.2 months). In the elraglusib/GnP group, patients with grade 3-4 TIN stayed on treatment significantly longer (median TTD: 7.9 months; P < 0.05) as compared to the patients who did not develop TIN grade 3-4 (median TTD: 1.7 months). Conclusions: Our preliminary results identified grade 3-4 TIN as a potential marker of improved clinical outcome for elraglusib/GnP therapy in previously untreated patients with mPDAC. Recruitment for the 1801 Part 3 Arm B phase 2 trial has been completed. Another interim analysis of OS and its correlation to grade 3-4 TIN will be available by April 2024 and will be included in the final presentation. Clinical trial information: NCT03678883 .
Longitudinal tissue-based evaluation of TIGIT expression in patients with pancreatic cancer: Effect of expression with advancing clinical stages and across racial groups.
Authors: George Madison , Clark Julie , Hartway Kailee , Zwernik Samuel , Gartrelle Kendyll , Sålas-Escabillas Daniel , Long Daniel , Nassif Georges , Pichardo Thais , Wombwell Allison , Wen Hui-Ju , Benitz Simone , Philip Philip A. , Khan Gazala , Shah Rupen A. , Park Hakmin , Crawford Howard , Kwon David S. , Theisen Brian , Steele Nina 
Published: July 2024

e16314 Background: While ground has been gained, pancreatic ductal adenocarcinoma (PDAC) continues to have a low 5-year survival of 13%. This is owed partially to a lack of early detection biomarkers and resistance to standard therapeutic options. TIGIT, an immune checkpoint receptor, is a marker of T-cell exhaustion and plays a key role in the inhibition of anti-tumor immune responses. TIGIT inhibitors are being explored in clinical trials in PDAC. Here we evaluate TIGIT expression in a cohort of PDAC patients and correlate level and intensity of expression with clinical parameters. We also examine changes in expression as the disease progresses from primary to metastatic disease. Methods: We performed RNAscope in situ hybridization (ISH) with a probe specific for human TIGIT mRNA on 82 formalin-fixed paraffin-embedded (FFPE) tissue samples. The cohort of tissue samples included 9 biopsies, 67 primary resections and 6 metastatic lesions. We evaluated the total TIGIT expression (%) as well as the intensity of TIGIT expression (% of cells with 3+ punctae, signifying putative immune cells), and compared these values between samples. Utilizing linear regression for continuous outcomes and logistic regression for binary outcomes, we tested for associations between TIGIT expression and clinical covariates. Results: Staining analysis showed that TIGIT expression did not differ significantly between racial groups. The mean percentage of TIGIT positive cells was 64.0%. High expression of TIGIT was associated with more advanced clinical stage (p < 0.05). Evaluation of three longitudinal samples from the same patient revealed decreased TIGIT expression from the initial biopsy (41.6%) to resection (33.4%) and metastasis (2.8%). In these specimens, 3+ TIGIT expression also declined (2.1%, 1.2% and 0.02%, respectively). Conclusions: Anti-TIGIT therapy has potential to reverse immune suppression and, with other therapeutic modalities, may provide survival benefit. Here we demonstrate that increased TIGIT expression correlates with more advanced stage at diagnosis and also present data demonstrating that overall TIGIT expression, as detected by RNAscope ISH, may decrease as PDAC progresses to metastasis. As such, anti-TIGIT therapy may have important implications for evading an important mechanism of cancer progression.
Demographic and socioeconomic analysis of patients with glucagonoma: Insights from the National Cancer Database.
Authors: Diagne Yaye Fatou , Alban Sierra , Reddy Nisha , Loomer Michael , Silberstein Peter T. , Heise Craig , Hsia Beau 
Published: July 2024

e16319 Background: Glucagonoma is a rare glucagon-producing alpha islet cell tumor primarily of the pancreas, and a type of pancreatic neuroendocrine tumor. These types of cancers have a 10-year survival rate of about 38%. Metastasis may be found in approximately 50% of glucagonoma cases. As a result of the low incidence of glucagonoma, analysis of the diagnostic patterns may provide more insight into the disease’s epidemiology. This study analyzed the National Cancer Database (NCDB) to examine demographic factors of individuals diagnosed with glucagonoma. Methods: ICD-8152-3 Data from the NCDB between 2004-2020 was gathered to perform a retrospective cohort analysis on patients diagnosed with glucagonoma (N = 88). Descriptive statistics were used to investigate demographic factors such as age, sex, race, Hispanic status, years of education, insurance, facility type, distance from facility, and Charlson-Deyo score. Regression analysis was utilized to evaluate incidence trends. Results: We found that patients had an average age of 61 years (SD = 13, range = 23-90), with an average tumor size of 53 mm (SD = 39, range = 12-140), and the majority were male (61%) and White (90%). The majority of patients (97%) did not receive palliative care, with surgery (57%) and chemotherapy (28%) being the primary treatments. Post-surgery, 90% had no residual tumor, and survival rates were 98% after thirty days and 96% after ninety days. Most were treated in academic/research facilities (43%) and had private insurance (59%) or Medicare (34%). The largest median household income quartile of these patients was $74,063 or more (39%).The study noted a 2-year survival rate of 74%, a 5-year rate of 54%, and a 10-year rate of 31%, with a mean survival of 89.3 months. The primary disease sites were the tail of the pancreas (32%) and pancreas, NOS (22%). The distribution across NCDB Analytic Stage Groups was 19% for Stage I, 11% for Stage II, 2% for Stage III, and 23% for Stage IV. Conclusions: This study represents the first analysis of glucagonoma patients using the National Cancer Database, filling a gap in our understanding of the disease. The findings indicate that the majority of glucagonoma patients were non-Hispanic, White, and had tumors primarily located in the tail of the pancreas, aligning with earlier case report descriptions. Socioeconomically, patients most likely had earnings above the median income quartile, resided in densely populated metropolitan areas, and received treatment in academic facilities. Further investigation is necessary to have a more thorough grasp of the impact of demographic and socioeconomic characteristics on glucagonoma patients' diagnosis, course of treatment, and overall survival rates.
Impact of acute ischemic stroke on mortality in gastrointestinal malignancies: A nationwide analysis.
Authors: Polpichai Natchaya , Saowapa Sakditad , Wattanachayakul Phuuwadith , Danpanichkul Pojsakorn , Fangsaard Panisara , Chan Shu-Yen , Chaisrimaneepan Nattanicha , Sirachainan Ekaphop 
Published: July 2024

e16372 Background: Acute ischemic stroke, marked by a sudden loss of brain blood supply, carries potential life-threatening consequences. The impact on individuals with pre-existing gastrointestinal (GI) malignancies, coupled with ensuing complex medical complications affecting morbidity and mortality, remains inadequately understood. This study aims to assess the influence of acute ischemic stroke on in-hospital mortality in GI cancer patients in the United States. Methods: This retrospective analysis utilized the 2016-2020 National Inpatient Survey (NIS) database. Adults aged 18 and above with esophageal, gastric, colon, cholangiocarcinoma, hepatocellular carcinoma, and pancreatic cancers were identified using the International Classification of Disease-10 (ICD-10) code. The cohort was stratified into patients with and without acute ischemic stroke. Hospital mortality was analyzed using STATA 18, adjusted for age, gender, race, insurance, Charlson’s index, baseline hospital characteristics, and comorbidities. Multivariate logistic regression analysis was performed, with all P values ≤ 0.05 considered statistically significant. Results: Among 2,133,465 adults with GI malignancies, 28,394 were hospitalized with acute ischemic stroke. Patients with acute ischemic stroke were older (mean age 71.19 vs. 67.01 years; P < 0.001), more likely to be male (55.47%, P = 0.002), Caucasian (67.96%, P < 0.001), from urban teaching hospitals (76.83%, P = 0.011), and had Medicare insurance (70.50%, P < 0.001). Acute ischemic stroke was most associated with pancreatic cancer (39.81%), colon cancer (30.13%), and esophageal cancer (9.86%). Within the cohort of patients with acute ischemic stroke, esophageal cancer patients had the highest mortality rates of 20%. After adjusting for potential confounders, patients with colon cancer, esophageal cancer, gastric cancer, pancreatic cancer, cholangiocarcinoma, and hepatocellular carcinoma had significantly higher odds of in-hospital mortality of 2.91, 2.50, 2.31, 2.22, 1.65, and 1.51, respectively. Conclusions: This study reveals an association between outcomes in hospitalized GI cancer patients and acute ischemic stroke, leading to increased mortality despite adjusting for potential confounders. The impact of anticancer therapies on the vascular system may influence the risk and severity of ischemic events. Further studies are needed to develop tailored prevention, diagnosis, and management strategies to reduce disease complications and the overall healthcare burden of cerebrovascular events.
Effect of NIR-II on cancer nanocomposite vaccines for lymph node targeted delivery and enhanced immunotherapy.
Authors: Zhou HaiYu , Huang YuCheng , Xu Bin , Hou HengLiang 
Published: July 2024

e20506 Background: Cancervaccines have become one of the hot areas of research in recent years. However, different types of tumors and the tumor tissue itself are heterogeneous. Some cancervaccines contain a single epitope and have weak immunogenicity. The antigen-presenting cells cannot adequately absorb and present the antigen peptide contained in the vaccine. As a result, the body fails to elicit an effective immune response, which greatly limits the therapeutic effect of the cancervaccine. In situ cancervaccines composed of antigens and adjuvants are a promising cancer treatment modality; however, convenient manufacturing of vaccines in vivo and their efficient delivery to lymph nodes (LNs) remain a significant challenge. In this study, we outline a facile approach to simultaneously achieve in situ programming of vaccines via two synergistic nanomedicines to generate robust immune responses. Methods: We first prepared two synergistic nanocomposite systems: Gold nanorods, amphiphilic polymer polyphosphate mPEG- b-PHEP encapsulating the immune adjuvant R848, and nanoparticles doped with cationic liposomes DOTAP. Two nanomedicines were characterized and the efficacy of the nanovaccine was verified at the Cellular Experiments. At the animal level, the lymph node targeting of the nanoparticles was demonstrated through IVIS. We also constructed distant model and lung metastasis model to verify the nanovaccine's effect on enhancing systemic immunotherapy. Results: We used amphiphilic polymer polyphosphate mPEG- b-PHEP to encapsulate TLR7/8 agonist R848 to obtain VNPR848 nanoparticles. Gold nanorods (~ 100nm) can produce a strong photothermal effect mediated by NIR-II, killing tumor cells and releasing abundant antigens at the same time. The small size of VNPR848 (~ 30nm) is beneficial to the enrichment of lymph nodes. After capturing the antigens produced by photothermal, nanoparticles will be targeted and delivered to the tumor draining lymph nodes together with R848, and will be effectively absorbed by DC cells. This in situ tumor vaccine with the ability of targeted delivery of lymph nodes can trigger a strong anti-tumor immune response. This therapy can completely inhibit distant tumors in some mice and produce a long-term immune memory effect on NSCLC metastasis. Conclusions: We propose a simple personalized in situ cancervaccine strategy, which uses nanotechnology to remove tumors in situ and release antigens. Antigens and immune adjuvants are simultaneously delivered to the draining lymph nodes to initiate the antigen presentation function of DC cells, resulting in an anti-tumor immune response to inhibit tumor recurrence and metastasis. The nano-vaccine based on powerful therapeutic effect provides an attractive technology for in situ programming of personalized cancervaccine and an effective strategy for the development of cancervaccine.
Analysis of the LIPI score as a prognostic factor in advanced non-small cell lung cancer.
Authors: Richardet Eduardo , Perea Pablo , Molina Matias , Magi Ignacio , Depetris Santos , Richardet Martin Eduardo 
Published: July 2024

e20612 Background: A field of interest is the search for new biomarkers within which inflammatory/immunological ones have taken on special relevance. The LIPI Score (Lung Immune Prognostic Index) that combines derived Neutrophil -Lymphocyte Ratio (dNRL) and LDH shows growing evidence in favor of its use. End Point: Primary: Evaluate the relationship of LIPI Score with Progression Free Survival (PFS) in advanced non-small cell lung cancer (NSCLC) treated with immunotherapy (IO) alone or in combinationwtih Chemotherapy(CT) in the first line. Secondary: Evaluate the relationship of the LIPI Score and Objective Response Rate (ORR) and the relationship of the LIPI Score and PFS at 6 months. Methods: Metastatic NSCLC , treated first-line with IO alone or in combination between January 2018 and July 2023 at our institution, were included . The LIPI Score has 3 prognosis categories: Good (RNLd &lt; 3 and LDH &lt; upper limit of normal (ULN) ); Intermediate (RNLd &gt; 3 or LDH &gt; upper limit of normal (ULN), Poor (RNLd &gt; 3 and LDH &gt; upper limit of normal (ULN) Results: 67 patients were analyzed, the overall PFS was 8.58 months. Of these, 22 had a good LIPI Score, 24 had an intermediate LIPI Score and 21 had a poor LIPI Score. The PFS per group was 21.56, 8.71 and 3.18 months respectively (p &lt; 0.01). The ORR was 27% in the general population and by groups: 45%, 29%, 5% respectively (p = 0.01). The 6-month PFS was 86%, 83% and 29%, respectively, by subgroup. Conclusions: We consider that the LIPI Score is a very useful tool due to its simplicity, low cost and accessibility that allows us to understand the behavior of the disease in our patients early. It is necessary to continue researching to determine what is the best therapeutic strategy for these patients based on their prognosis.