bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of immune biomarkers in treatment-naive patients with metastatic pancreatic cancer treated with the GSK-3 inhibitor elraglusib (9-ING-41) in combination with gemcitabine/nab-paclitaxel in the 1801 phase 2 study.
Authors: Weiskittel Taylor , Koukol Austin , Kellinger Caroline , Zhang Leiqing , Carneiro Benedito A. , Li Hu , Ugolkov Andrey , El-Deiry Wafik S. , Mazar Andrew Paul 
Published: July 2024

e16331 Background: Elraglusib (9-ING-41), a potent and selective GSK-3 inhibitor, is a targeted anticancer agent with clinical activity in phase 1 trial and undergoing clinical development for the treatment of metastatic pancreatic ductal adenocarcinoma (mPDAC). Elraglusib (9-ING-41) displayed immune-modulatory activity in preclinical models and modulation of serum cytokine profile in clinical specimens. Here, we investigated the correlation between plasma levels of cytokines/chemokines/soluble cell receptors/growth factors (CCSG) and clinical outcomes of patients with mPDAC treated with elraglusib and gemcitabine/nab-paclitaxel (GnP) in an exploratory study. Methods: CCSGs were evaluated in the pre-dose plasma samples of patients with newly diagnosed mPDAC enrolled in the 1801 phase 2 study (NCT03678883) treated with GnP (n = 13) or elraglusib/GnP (n = 32). Using a Luminex immunoassay, 40 CCSGs were screened as predictive biomarkers of median overall survival (mOS) in the elraglusib/GnP arm using 5-fold cross-validation and maximally selected rank statistic cutpoint determination. A subset of CCSGs (n = 10) was remeasured using an MSD immunoassay with greater sensitivity. Maximally selected rank statistic cutpoint determinations were conducted using MSD results for elraglusib/GnP samples with mOS and median progression free survival (mPFS). P values < 0.05 were considered statistically significant. Results: Luminex screening revealed several CCSGs significantly stratified elraglusib/GnP patients by mOS. IL-6 and IL-8 were identified as top candidates with stable and significant results on cross-validation. Using the MSD assay, both were confirmed to stratify elraglusib/GnP patients by OS and extended to analyze PFS. Low level of IL-8 conferred a better OS prognosis (HR: 0.0919, 95%, CI: 0.0205-0.411, P < 0.001) than low IL-6 (HR: 0.205, 95%, CI: 0.063-0.665, P = 0.005) in the elraglusib/GnP treated patients. Correlations with mPFS were similar in the elraglusib/GnP patients for IL-6 (HR: 0.248, 95% CI: 0.072-0.848, P = 0.02) and IL-8 (HR: 0.297, 95%, CI: 0.111-0.743, P = 0.01). Conclusions: Preliminary results of our exploratory study identified low plasma levels of IL-6 and IL-8 prior to elraglusib/GnP treatment as potential predictive biomarkers associated with improved outcomes in previously untreated patients with mPDAC. The 1801 Part 3 Arm B clinical trial recruitment has been completed. We plan to analyze additional pre-dose plasma samples obtained from approximately 200 patients by April 2024. These will be analyzed using interim OS data available by April 2024 and included in the final presentation. Clinical trial information: NCT03678883 .
Impact of treatment setting on survival outcomes in undifferentiated pancreatic carcinoma: An analysis of the National Cancer Database.
Authors: Braun John Paul , Bine Christopher Reese , Silberstein Peter T. 
Published: July 2024

e16333 Background: Undifferentiated carcinoma of the pancreas is a rare and highly aggressive form of pancreatic cancer, characterized by its low degree of cellular differentiation. The prognosis for this condition remains poor, with median survival times typically not exceeding one year. While existing research indicates that treatment at academic institutions may lead to improved survival outcomes compared to non-academic settings, there is scant research on this topic in the context of undifferentiated carcinoma of the pancreas. Addressing this research gap, this study analyzes data from the National Cancer Database (NCDB) to compare long-term survival rates between patients treated at academic institutions and those at other facilities. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with undifferentiated carcinoma of the pancreas from 2004 to 2019 using the histology code 8020 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA, and Chi-Square tests were performed. Data was analyzed using SPSS version 27 and statistical significance was set at α = 0.05. Results: In this analysis of 284 patients, 124 (43.7%) received care at academic centers, while 160 (56.3%) were treated at non-academic institutions. Individuals treated at academic centers had a significantly extended mean overall survival of 27 months compared to 13.9 months for those treated elsewhere (p < 0.05). Additionally, patients at academic centers were more likely to be insured, undergo surgical interventions, receive chemotherapy, and be initially diagnosed at a different facility (p < 0.05). Conversely, patients at non-academic centers were more likely to be white, live closer to their care facility, and exhibit greater metastatic regional lymph nodes (p < 0.05). However, there was no significant association between treatment at academic centers and variables such as median income, cancer grade, and Charlson-Deyo Comorbidity Index (CDCI) (p > 0.05). Conclusions: This study revealed that individuals with undifferentiated carcinoma of the pancreas receiving treatment at academic centers exhibit a significantly improved overall survival rate compared to those treated at non-academic centers. This disparity in survival rates might be attributed to the higher prevalence of chemotherapeutic treatments and surgical interventions at academic institutions. While these observations are based on correlational data, they underscore the necessity for further investigation to establish causality.
Molecular and clinical features of pancreatic acinar cell carcinoma: A single institutional experience.
Authors: Balachandran Pillai Ashwathy , Yousef Mahmoud M.G. , Yousef Abdelrahman M.G. , Hurd Mark W. , Wang Huamin , Maitra Anirban , Willis Jason , Shen John Paul Y.C. , Pant Shubham , Smaglo Brandon George , Wolff Robert A. , Zhao Dan 
Published: July 2024

e16335 Background: Acinar Cell Carcinoma (ACC) accounts for around 1% of pancreatic cancer. The molecular and clinical features of acinar cell carcinoma are less characterized. We sought to evaluate the clinical and molecular features of patients with ACC at MD Anderson Cancer Center. Methods: Patients with ACC who had germline and/or somatic molecular testing at MD Anderson Cancer Center from 2008 to 2022 were identified retrospectively. After obtaining approval of approval of the institutional review board genomic alterations including germline or somatic BRCA mutations, KRAS mutation, demographic, clinical, and pathological information were extracted from institutional databases using the Palantir Foundry software platform (Syntropy); this included natural language processing with subsequent validation by manual chart review. Overall Survival (OS) was calculated from the date of diagnosis to death or last follow-up. The Kaplan-Meier method was used for survival analysis. Results: 16 patients were identified with molecular testing results available. There were 13 males and 3 females. The median age of diagnosis was 62.5 years (range 49 -72). 14/16 patients (87.5%) had metastatic disease, one (6.25%) patient had borderline resectable disease and one (6.25%) had localized resectable disease at initial diagnosis. Median OS was for 24 months for patients with metastatic disease. There were 2 patients with mixed pathology, 1 with acinar cell carcinoma with neuroendocrine features and the 2nd had mixed acinar cell-ductal carcinoma. 15/16 (93.75%) patients were tested for KRAS and all 15 were KRAS wildtype. Somatic mutations in DNA damage repair genes (BRCA2, PALB2) were present in 3 patients (25%) and 2 patients had germline mutation (BRCA and ATM) (16%) out of 12 patients tested for those genes. 6/16 (37.5%) patients were treated with FOLFIRINOX at first line. 3/6 (50%) of these patients had partial response, 2/6 (33%) had stable disease and only 1/6 (16%) had progression. 5 patients were treated with FOLFOX based regimen and 1/5 (20%) had response, 2/5 (40%) had stable disease and 2/5 (40%) had progression of disease. 5 patients were treated with gemcitabine-based regimen and only 1 had response which received gemcitabine/nab-paclitaxel combined with cisplatin. Conclusions: ACC were KRAS wild type and had higher rates of germline/somatic mutations in DNA damage repair genes. Better treatment outcome of FOLFIRNIOX/ platinum-based regimens was suggested based on this limited patient dataset. Larger studies are needed to further understand the molecular features of ACC and guide the treatment of this rare entity of pancreatic cancer.
Correlation of significant delays and ethnic disparities in the receipt of treatment, palliative care, and supportive care interventions in pancreatic adenocarcinoma.
Authors: Gupta Aakash Rai , Richards Jefferson , Sakai Leo , Al-Manaseer Farris , Nguyen Brian , Miles Ethan , Cote Gregory Michael , Ferrell Betty R. , Joachim-Celestin Maud , Montgomery Susanne , Saumoy Monica , Reeves Mark Evan , Thiruvengadam Nikhil Ravi 
Published: July 2024

e16355 Background: In patients with pancreatic adenocarcinoma (PDAC), immediate treatment initiation is preferred. Early palliative care initiation has also improved quality of life and symptom burden. However, the timing of real-world treatment and palliative care initiation and possible ethnic disparities are not well understood. The objective of this study was to evaluate the timing of care initiation in a mainly Hispanic population of PDAC patients. Methods: We conducted a retrospective cohort study that included patients diagnosed with PDAC from 2014 to 2023 at Loma Linda University Health (the only tertiary care center for two large Hispanic-majority counties with large rural populations). Data were obtained on the presence and timing of appropriate provider referrals, care establishment, treatment, advanced care planning, and hospital admissions. We used a Wilcoxon rank-sum test to compare Hispanic and non-Hispanic patients regarding the time to treatment initiation and palliative care initiation. Results: 263 PDAC patients were identified (mean age 66, 57% female, 47% Hispanic, 67% head tumor, 78% stage III/IV). After diagnosis, 93% of patients were referred to medical oncology, 82% to surgical oncology, 61% to palliative care, and 30% to genetic testing. An advanced directive or physician orders for life-sustaining treatment was completed for 24% of patients. The time to care initiation is as follows: a median of 23 days (IQR 14, 54) from diagnosis to the first medical oncology visit, 13 days (IQR 6, 37) to the first surgical oncology visit, 73 days (IQR 24, 132) to the first palliative care visit and 133 days (IQR 47, 329) to hospice referral. 64% of hospice referrals were placed within the last two weeks of life. Hispanic patients had a significantly longer time to treatment initiation (68 days vs. 48 days, p= 0.008) but similar times to palliative care initiation (73 vs 74 days, p= 0.64). Hispanics also had a lower rate of completing genetic testing (45% to 66%, p= 0.07). Conclusions: In our retrospective cohort study, significant delays in establishing care with oncology, palliative care, and hospice initiation in patients with PDAC were noted. Low rates of advanced care planning were also noted despite guideline recommendations for early-focused symptomatic interventions and advanced care planning. Hispanic patients had significantly longer time to treatment initiation and lower rates of genetic testing. These results indicate a need for improved targeted patient care navigation for multidisciplinary PDAC management, particularly in Hispanic patients.
An NCDB analysis of the predictive factors associated with the receival of tumor resection in mucinous cystadenoma of the pancreas.
Authors: Devireddy Shalika , Silberstein Peter T. , Chaddha Jasleen Kaur 
Published: July 2024

e16356 Background: Mucinous cystadenoma (MCN) of the pancreas is characterized by mucin-producing cystic tumors that may lead to pancreatic ductal obstruction. While many of these cystic lesions are benign, there exists a notable risk for malignancy. Presently, the standard approach to managing MCN involves surveillance. Surgical resection is considered after evaluating histological features, the patient's age, surgical risk, and tumor size. Previous studies have linked surgical resection to favorable overall outcomes. However, no studies have investigated the predictive factors correlated to receiving surgery in MCN patients. This study aims to utilize the National Cancer Database (NCDB) to analyze factors that determine receival of tumor resection in patients with MCN of the pancreas. Methods: The NCDB was used to identify patients diagnosed with MCN of the pancreas from 2004 to 2019 using the histology codes 8470 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Multilevel Logistic Regression were performed, and data were analyzed using SPSS version 27. Statistical significance was set at α = 0.05. Results: 827 patients with MCN of the pancreas formed the initial sample. 552 patients received a tumor resection whereas 274 patients did not receive surgery ( 66.7% vs 33.1%, respectively). Surgical patients experienced significantly longer overall survival than nonsurgical patients ( 111.2 months vs. 20.1 months, p < 0.001). Complete tumor resection with no residual tumor cells was associated with improved outcomes in MCN( p < 0.001). Metastasis to distant sites was associated with decreased likelihood of receiving surgery ( p < 0.001). Well and moderately differentiated disease, stage I, II, and II disease, treatment at an academic facility, and private insurance status were associated with increased likelihood of receiving tumor resection ( p < 0.001). Income status and race did not appear to impact overall survival of these patients. Adjuvant therapies did not appear to impact overall survival of these patients. Conclusions: The results of this research align with other studies, affirming that surgical resection yields superior outcomes in patients with MCN of the pancreas. Factors such as well or moderately differentiated disease, early-stage diagnosis, treatment at academic facilities, and private insurance status increased the likelihood of tumor resection. Distant metastasis reduced the likelihood of receiving surgery. Complete tumor removal without presence of residual tumor cells post-surgery is correlated with improved survival. Income status and race did not appear to impact overall survival, and adjuvant therapies showed no discernible effect. To improve current treatment protocols for patients with MCN of the pancreas, more research needs to be conducted on the predictive factors of receiving surgery.
Experience of seven Spanish centres with echoendoscopically implanted 32P microparticles associated with chemotherapy in locally advanced pancreatic adenocarcinoma.
Authors: Guillen-Ponce Carmen , Lopez-Gomez Victoria , Juez Ignacio , Navales Ignacio , Ponz-Sarvise Mariano , Adeva Jorge , Rodriguez Cernuda Maria Purificacion , Garrido Maria , Garcia Garcia De Paredes Ana , Zamora Javier 
Published: July 2024

e16358 Background: 32P brachytherapy delivered by echoendoscopy (EUS) represents an innovative therapy in locally advanced pancreatic cancer (LAPC). The device to implant it is approved in unresectable LAPC in combination with gemcitabine-based chemotherapy. Our aim is to present the preliminary efficacy and safety results of a series that brings together the experience of seven centres in Spain. Methods: After being assessed by a multidisciplinary committee and meeting eligibility criteria (Table 1), patients signed consent to receive intratumoural 32P by EUS within the international observational registry OSPREY (March 2022-February 2024). Complications associated with intratumoural 32P injection via EUS, associated adverse events (AEs) and preliminary efficacy results (progression-free survival [PFS], distant and locoregional, and overall survival [OS]) were analysed. Results: Thirteen patients (7 females; age 65 years [range 48, 79]; 10 ECOG 1) with unresectable LAPC (7 in head, 3 in uncinate and 3 in body; tumour size 36.8 mm [range 25, 60]) were included. The median time from tumour diagnosis to procedure was 5 months [1.4, 28.9]. Only 4 patients (30 %) had received a previous line of treatment. Eleven patients (85%) received gemcitabine-based chemotherapy concomitant with intratumoural 32P (8 gemcitabine plus nabpaclitaxel; 3 gemcitabine monotherapy). There were no complications or AEs related to 32P injection or EUS. A total of 7 patients (54%) had chemotherapy-related AEs, with 2 cases of G3 neutropenia; 6 had G1-2 toxicities: neutropenia (1), thrombopenia (2), anaemia (1), nausea (1), asthenia (1), diarrhoea (1) and constipation (1). Two patients underwent surgery after intratumoural treatment. With a median follow-up of 17.3 months after injection, 8 patients (61.5 %) have progressed, all of them distantly, and three also locoregionally. The median PFS since 32P injection is 8.4 months (95% CI 2.7, NR). Six patients are alive at the end of follow-up (46.2 %) with a median OS since 32P injection of 13.8 months 95% CI [10, NR]. At data cut-off, five patients remain on-treatment. Conclusions: Our initial experience suggests that intratumoural 32P associated with gemcitabine-based chemotherapy is safe. Patients after 32P injection achieve long overall survival. Our ongoing prospective registry will allow evaluation of the oncological outcomes of this therapy at longer follow-up times. [Table: see text]
Analyzing imbalance of short tandem repeats for pancreatic cancer detection.
Authors: Levine Jonathan , Finkelstein Sydney , Timmaraju Venkata Arun 
Published: July 2024

e16359 Background: Short tandem repeats (STRs), alternatively known as microsatellites, encompass repeat units of 1 to 6 base pairs (bp) in the genome and function as regulators of gene expression, impacting plasticity and complex traits. STRs are prone to hypermutation with alterations correlated to pathogenicity in multiple Mendelian and acquired disorders. STR variant classes include insertions, mobile element insertions (MEIs), deletions, and multi-allelic copy number variants (mCNVs). These can lead to repeat expansions, allelic imbalance (AI), and microsatellite instability (MSI) observed in diseases such as Huntington's disease, hereditary ataxia, and multiple cancers. In pancreatic cancer, AI and associated loss-of-heterozygosity (LOH) at tumor suppressor loci flanked by hypervariable STR regions correspond to a pathogenic phenotype with a risk of aggressive disease. Consequently, it is critical to develop accurate and robust methods to precisely identify and genotype pancreatic samples with varying specimen quality in a clinical setting to aid in diagnosis. Methods: Capillary electrophoresis (CE) and Sanger sequencing have been used to analyze STRs. The availability of newer tools such as 2nd generation short-read (NGS) and 3rd generation long-read (TGS) sequencers could allow for high throughput scaling, however, informatics challenges associated with analyzing repetitive regions remain. Here we developed amplification and enrichment methods for targeted analysis for detection by CE, NGS and TGS. Results: Amplification and enrichment strategies for detecting 17 short tandem repeat regions that play a role in pancreatic carcinogenesis were developed. Methods were optimized for detecting STR alterations in cell-free nucleic acids isolated from endoscope-guided pancreatic fine needle aspirate biopsies. Furthermore, informatics tools were developed to analyze short-read and long-read sequencing data to accurately analyze repeat regions. Conclusions: Here we compared 3 platforms (CE, NGS, and TGS) and found that CE remains the gold standard for analyzing AI/LOH with data comparable to long-read TGS, while short-read NGS is not always amenable to accurate analysis dependent on the region of interest. Additionally, we found that artifacts of amplification persist, irrespective of the 3 platforms analyzed.
Recurrence patterns and surveillance strategies in long-term survivors of resected pancreatic cancer.
Authors: May Michael S. , Stanton Liam James , Jamison Jacob K. , May Benjamin , Michel Alissa M. , Raufi Alexander G. , Wong Winston , Kastrinos Fay , Accordino Melissa Kate , Hershman Dawn L. , Manji Gulam Abbas , Wu Linda 
Published: July 2024

e16361 Background: Pancreatic ductal adenocarcinoma (PDA) is the third leading cause of cancer-related mortality in the United States. After resection, the 2-year disease-free survival is < 50%. Surveillance guidelines after resection vary significantly between expert groups. The level of evidence is particularly weak for patients who are alive and disease-free after 2 years. Our objective was to report rates and predictors of recurrence in this population. Methods: We reviewed all patients who underwent resection of stage I-III PDA at Columbia University Irving Medical Center from 2011-2022. Eligibility criteria included patients who were alive and disease-free at 2 years after diagnosis. Demographic, surgical, and treatment characteristics were recorded. Imaging studies and tumor markers were reviewed and median time between studies after 2 years of follow up was determined. Recurrence was confirmed histologically or radiologically. Follow up and survival times were calculated using Kaplan Meier statistics. Associations between patient characteristics and recurrence risk were evaluated using a Cox proportional-hazards regression adjusted for demographic and treatment characteristics. Results: We reviewed 743 patients and 225 met eligibility criteria. The median age at diagnosis was 67.5 years. Median interval between surveillance imaging was 59 days and median interval between CA 19-9 draws was 41 days. After a median follow-up of 5.2 years from diagnosis, 84/225 (37%) patients experienced a late recurrence. Of these, 35% (29/84) had local recurrence, and 65% (55/84) had distant recurrence. The most common distant sites were lung (51%) and liver (27%). Lymph node positivity at resection was associated with late recurrence risk (p = 6x10-6), but T-stage (p = 0.5), margins (p = 0.9), age (p = 0.2) and chemotherapy receipt (p = 0.3) were not. Of the 72 patients with CA 19-9-producing tumors (baseline CA 19-9 > 37 U/mL) and complete normalization of CA 19-9 postoperatively, 30 patients had recurrence with CA 19-9 checked in the 9 months preceding recurrence. CA 19-9 re-elevation preceded recurrence in 83% (25/30) of late recurrences. Median time from CA 19-9 elevation to confirmation of recurrence was 5 months. Conclusions: The rate of recurrence for patients with PDA who are disease-free 2 years after diagnosis is lower than that for patients in their first 2 years. The most common sites of late recurrence are local and lung. For long-term PDA survivors with CA 19-9 producing tumors, serial CA 19-9 monitoring may be used to guide imaging. Positive lymph nodes at resection identify patients who are at highest risk for late recurrence.