Outcomes In Pancreatic Cancer Research Articles

Impact of an Inter-Professional Clinic on Pancreatic Cancer Outcomes: A Retrospective Cohort Study.

Background: Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges in diagnosis, staging, and appropriate treatment. Furthermore, patients with PDAC often experience complex symptomatology and psychosocial implications that require multi-disciplinary and inter-professional supportive care management from health professionals. Despite these hurdles, the implementation of inter-professional clinic approaches showed promise in enhancing clinical outcomes. To assess the effectiveness of such an approach, we examined the impact of the Wallace McCain Centre for Pancreatic Cancer (WMCPC), an inter-professional clinic for patients with PDAC at the Princess Margaret Cancer Centre (PM). Methods: This retrospective cohort study included all patients diagnosed with PDAC who were seen at the PM before (July 2012-June 2014) and after (July 2014-June 2016) the establishment of the WMCPC. Standard therapies such as surgery, chemotherapy, and radiation therapy remained consistent across both time periods. The cohorts were compared in terms of survival rates, disease stage, referral patterns, time to treatment, symptoms, and the proportion of patients assessed and supported by nursing and allied health professionals. Results: A total of 993 patients were included in the review, comprising 482 patients pre-WMCPC and 511 patients post-WMCPC. In the multivariate analysis, adjusting for ECOG (Eastern Cooperative Oncology Group) and stage, it was found that post-WMCPC patients experienced longer median overall survival (mOS, HR 0.84, 95% CI 0.72-0.98, p = 0.023). Furthermore, the time from referral to initial consultation date decreased significantly from 13.4 to 8.8 days in the post-WMCPC cohort (p < 0.001), along with a reduction in the time from the first clinic appointment to biopsy (14 vs. 8 days, p = 0.022). Additionally, patient-reported well-being scores showed improvement in the post-WMCPC cohort (p = 0.02), and these patients were more frequently attended to by nursing and allied health professionals (p < 0.001). Conclusions: The implementation of an inter-professional clinic for patients diagnosed with PDAC led to improvements in overall survival, patient-reported well-being, time to initial assessment visit and pathological diagnosis, and symptom management. These findings advocate for the adoption of an inter-professional clinic model in the treatment of patients with PDAC.

The Molecular Characteristics and Therapeutic Implications of O-Glycan Synthesis in Pancreatic Cancer by Integrating Transcriptome and Single-Cell Data.

Glycans constitute the primary components of proteins that regulate key carcinogenic processes in cancer progression. This study investigated the significance of O-glycan synthesis in the pathogenesis, outcome, and therapy of pancreatic cancer (PC). Transcriptomic data and clinical prognostic information of PC were acquired via TCGA and GEO databases. CSA database was used to obtain single-cell data of PC. The O-glycan biosynthesis signaling pathway and its related genes were acquired via the MSigDB platform. The nonnegative matrix factorization (NMF) clustering was utilized to construct the O-glycan biosynthesis-associated molecular subtypes in PC. The LASSO and Cox regression were utilized to build the prognostic prediction model. We utilized real-time quantitative PCR (qRT-PCR) to verify the expressed levels of model genes. Single-cell analysis was utilized to investigate the levels of target genes and O-glycan biosynthesis signaling pathway in the PC tumour microenvironment. We obtained 30 genes related to O-glycan biosynthesis, among which 15 were associated with the prognosis of PC. All PC samples were grouped into two distinct molecular subtypes associated with O-glycan biosynthesis: OGRGcluster C1 and OGRGcluster C2, and compared to OGRGcluster C1. PCs in OGRGcluster C2 had a more advanced clinical stage and pathological grade, worse prognosis, and more active O-glycan biosynthesis function. Immune analysis indicated that naïve B cell, CD8+ T cell, memory-activated CD4+ T cell, and monocytes displayed remarkably higher infiltration levels in OGRGcluster C1 while resting NK cell, macrophages M0, resting dendritic cell, activated dendritic cell, and neutrophils exhibited markedly higher infiltration levels in OGRGcluster C2. OGRGcluster C1 exhibited higher sensitivities to drugs, such as cisplatin, irinotecan, KRAS(G12C) inhibitor-12, oxaliplatin, paclitaxel, and sorafenib. Besides, we built the O-glycan biosynthesis-related prognostic model (including SPRR1B, COL17A1, and ECT2) with a good prediction performance. SPRR1B, COL17A1, and ECT2 were remarkably highly expressed in PC tissues and linked to a poor outcome. Single-cell analysis revealed that Oglycan biosynthesis was observed only in PC, and consistent with this, the target genes were significantly enriched in PC. We first constructed molecular subtypes and prognostic models related to O-glycan biosynthesis in PC. It is clear that O-glycan biosynthesis is related to the development, prognosis, immune microenvironment, and treatment of PC. This provides new strategies for stratification, diagnosis, and treatment of PC patients.

Management Modalities of Pancreatic Cancer and Surgical Outcomes of Braun's Anastomosis Addition in Whipple's Procedure: A Single-center Prospective Study

Background: Pancreatic cancer is an aggressive malignancy with high mortality rate. Many morbidities associated with Whipple's procedure that endanger patients’ life which need updated surgical techniques to lower these morbidities. The aim of this study is to determine management modalities of pancreatic cancer and surgical outcomes of adding Braun's jejunojejunostomy to Whipple's procedure for reduction of postoperative risks in Sudanese patients to reach excellent surgical practice. Subjects and Methods: This is a prospective-cohort study conducted during the period between January 2022 and July 2023 at Ibn Sina specialized hospital, Khartoum, Sudan, on sixty-three patients diagnosed with resectable pancreatic cancer. Addition of Braun’s jejunojejunostomy to elective open Whipple’s surgery was performed. Results: Seventy-three percent of patients diagnosed with pancreatic cancer were males with the ratio (3:1). Patients’ distribution according to age ranged between 46 and 60 years representing (41.3%). The significant reported comorbidities that associated with PC were diabetes mellitus (30.2%) and businessmen (39.7%). Most of patients were lived in rural areas (57.1%). Abdominopelvic CT-scan revealed stage (II) of pancreatic cancer in (68.2%) of patients. The predominant morbidity after addition of Braun's jejunojejunostomy was wound infections noticed in (17.5%) of patients. Moreover, other complications were categorized as follows: pulmonary infections in (6.35 %) of cases, postoperative diabetes mellitus in (4.76 %) of cases, entero-cutaneous fistula in (4.76 %) of cases, delayed gastric emptying in (3.17%) of cases, biliary leak in (3.17%) of cases, (3.17%) of cases, pancreatic fistula in one case (1.58%), gastric outlet obstruction in one case (1.58%) and postoperative GIT bleeding in one case (1.58%). Postoperative hospital stay of patients were ranged between 8-15 days for (66.7%) of cases. The mortality rate was zero. Conclusions: To reduce the rate of lethal surgical morbidities of Whipple's procedure, we recommend addition of Braun's jejunojejunostomy as useful technique. Moreover, it will potentially help in improving the quality of surgical practice and survival outcomes of patients who diagnosed with pancreatic cancer.

Abstract 2545: KRAS co-mutational landscape dictates treatment outcomes in pancreatic cancer (PC) patients

Abstract Background: KRAS is commonly mutated in PC patients, with a prevalence of ~80%. A holistic understanding of the landscape of KRAS mutations, co-occurring mutations (co-mutations) in other driver genes, and their impact on patient outcomes treated with current standard-of-care (SoC) therapies may inform better treatment decisions. Methods: In this study, we use a real-world clinico-genomics PC database (ConcertAI’s Genome360TM PC dataset; N=1302) to:1.Examine the distribution of KRAS mutations.2.Identify the genes most frequently co-mutated with KRAS, both positively and negatively, based on their odds ratios.3.Evaluate patient outcomes (overall survival (OS) and progression-free survival (PFS)) for the two most common first-line SoC therapies (FOLFIRINOX: folinic acid, fluorouracil, irinotecan hydrochloride, oxaliplatin, and GEMPAC: gemcitabine, paclitaxel) stratified by the mutational status of KRAS and TP53. Results: The top 5 most observed KRAS mutations and the top 3 positively (OR&amp;gt;1) and negatively (OR&amp;lt;1) KRAS co-mutated genes are shown in Table 1. 80%, 71%, and 65% of PC patients had pathogenic mutations in KRAS, TP53, and both genes, respectively. In the entire cohort, FOLFIRINOX (n=327, OS/PFS=1.26/0.58 years) was more effective (p-value&amp;lt;0.05) than GEMPAC (n=305, OS/PFS=0.79/0.44 years). However, the underlying genetic makeup (mutational status of KRAS and TP53) significantly affects these outcomes (Table 1). The KRAS+/TP53− (pathogenic mutations in KRAS, but not in TP53) cohort has the worst prognosis, and the advantage of FOLFIRINOX as the treatment of choice is not observed in this cohort. Table 1. Evaluation of KRAS mutational landscape in PC and its impact on treatment outcomes. Top 5 KRAS mutations KRAS mutations G12D G12V G12R Q61H Q61R % PC patients tested positive 42.51 32.52 14.33 4.62 1.79 Top 3 positively and negatively co-mutated genes with KRAS KRAS co-mutated genes Positive association Negative association TP53 CDKN2A SMAD4 BRAF TERT PTEN Odds Ratio 8.56 6.93 6.66 0.05 0.27 0.32 Treatment outcomes for various genetic states of KRAS and TP53 Mutational status OS (years) PFS (years) FOLFIRINOX GEMPAC FOLFIRINOX GEMPAC KRAS+ TP53+ (850) 1.13 (196) 0.68 (188) 0.58 (196) 0.39 (188) KRAS− TP53− (155) 2.08 (40) 1.11 (27) 0.66 (40) 0.51 (27) KRAS+ TP53− (190) 0.77 (33) 0.93 (37) 0.51 (33) 0.33 (37) KRAS− TP53+ (81) 2.14 (15) 0.84 (24) 0.54 (15) 0.4 (24) Conclusions: This study provides insights into the genetic makeup of patients with KRAS mutations and how co-mutation with TP53 affects outcomes of SoC treatments. It highlights the need for comprehensive genetic profiling to make better therapy decisions. Citation Format: Pritha Ghosh, Rohini George, Neeraj Singh, Smita Agrawal. KRAS co-mutational landscape dictates treatment outcomes in pancreatic cancer (PC) patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2545.

Abstract 2145: Genetic ancestry associations with pancreatic cancer mutational profiles from a diverse 9,274-patient real-world cohort

Abstract Pancreatic cancer is an aggressive malignancy associated with racial/ethnic disparities. Notably, Black patients have a higher incidence and mortality compared to their White counterparts. However, low representation of Black and Hispanic patients in cancer genomics studies hampers our understanding of genomic factors contributing to differential outcomes. Furthermore, comparisons between racial groups fail to capture differences in genomic ancestry. We studied the associations between genetic ancestry and race/ethnicity categories with mutational profiles, using a large, diverse real-world pancreatic cancer cohort. We analyzed 9,274 de-identified pancreatic cancer patients (8,483 with ductal adenocarcinoma, PDAC) who underwent tumor profiling with the Tempus xT 648-gene assay. We used 654 ancestry-informative markers to estimate continental ancestry for five regions: Africa (AFR), Americas (AMR), East Asia (EAS), Europe (EUR), and South Asia (SAS). We imputed Asian (ASN, n=431), Hispanic/Latino/Native American (HLN, n=593), Non-Hispanic Black (NHB, n=875) and Non-Hispanic White (NHW, n=7,309) categories from genetic ancestry using a previously published machine learning method. Associations between either race/ethnicity categories or ancestry proportions and somatic variants (copy number alterations or CNAs, small nonsynonymous, OncoKB L1/2 &amp; R1, and predicted driver somatic mutations using boostDM) were assessed for 172 pancreatic cancer-related genes or gene sets using logistic regression models. Models with and without race/ethnicity or ancestry terms were compared with likelihood ratio (LR) tests, and p-values were adjusted to control the FDR at 5%. We tested for associations of race/ethnicity groups with TMB using a Kruskal-Wallis rank sum test. Tests of TMB and small variants used only patients with available matched normal tissue to avoid artifacts from misclassification of germline variants. Among pancreatic cancer patients, having either a CNA or small nonsynonymous mutation in a receptor tyrosine kinase (RTK) gene (ERBB2, EGFR, MET, FGFR1) was associated with genetic ancestry (LR adjusted p=0.027). Specifically, AMR ancestry was positively associated (OR=1.08 per doubling of ancestry proportion, p=0.004) and EUR negatively associated (OR=0.93, p=0.002). Associations in PDAC were similar but not significant. Race/ethnicity was associated with RTK changes in both groups, with ASN and HLN having more mutations than NHW, but the associations were not significant after correcting for multiple hypotheses. There was no association of race/ethnicity and TMB .Somatic changes in RTK genes were associated with AMR genetic ancestry; however, despite the relatively large cohort size, these results are modest, suggesting there is not a large somatic mutation component contributing to differences in pancreatic cancer outcomes by ancestry. Citation Format: Brooke Rhead, Vignesh Vudatha, Yannick Pouliot, Edward Williamns, Andrea N. Riner, Francisco M. De La Vega, Jose Trevino. Genetic ancestry associations with pancreatic cancer mutational profiles from a diverse 9,274-patient real-world cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2145.

Abstract 6470: Real-world analysis of insurance status and survival in patients with selected GI cancers

Abstract Background: Health insurance is a critical determinant of healthcare access and outcomes in gastrointestinal (GI) cancers. Epidemiological data have shown that insurance-associated healthcare outcomes vary by diagnosis, geographic location, and demographics. Thus, it is critical for cancer providers to understand local impacts of insurance status on patient outcomes. Here, we present real-world outcomes for pancreatic, hepatobiliary, and colorectal cancer (CRC) patients in 11 Midwest hospitals based on insurance status. Methods: We identified patients diagnosed with colorectal, pancreatic, and hepatobiliary cancers within 11 Midwest hospitals from 2011-2021 with North American Association of Central Cancer Registries data. Health insurance was defined as private, Medicaid, Medicare, and uninsured. Effect of insurance status at diagnosis on overall survival (OS) in selected cancers combined and by cancer type were calculated using a Cox proportional hazard (CoxPH) model controlling for age, sex, race, stage, time to treatment initiation (TTI), and Charlson Comorbidity Index (CCI). We evaluated differences in TTI by insurance status using t-tests. We analyzed stage and treatment modality by insurance status using chi-square tests. Post-hoc analysis of TTI by OS used CoxPH. Results: Relative to private insurance, Medicaid and Medicare insurance status significantly reduced OS for all selected GI cancers combined (HR 1.38, 95% CI 1.17 - 1.62 and HR 1.25, 95% CI 1.11 - 1.40, respectively; p&amp;lt;0.001) and for CRC (HR 1.49, 95% CI 1.12 - 1.98 and HR 1.28, 95% CI 1.06 - 1.54, respectively; p&amp;lt;0.01). Uninsured patients had significantly reduced OS only for pancreas cancer (HR 6.36, 95% CI 2.56 - 15.8; p&amp;lt;0.001). No significant associations between insurance status and OS were noted in Hepatobiliary cancer. TTI was significantly associated with insurance status (p&amp;lt;0.001) and mean TTI for Medicaid (35.8 days) and Medicare (27.9 days) patients was longer than mean TTI for privately insured patients (23.3 days; p&amp;lt;0.01). TTI for uninsured patients was not significantly different than for privately insured. Analysis of TTI and OS showed no increased hazard for patients with TTI of 36 days versus 23 days (HR 0.87, 95% CI 0.75 - 1.02; p=0.085). Treatment modality and stage did not differ as a function of insurance status in this dataset. Discussion: Our results expand previous work by demonstrating a survival impact for GI cancer patients with Medicaid or Medicare insurance. This disparity persists despite controlling for known prognostic factors such as age, stage, CCI, and TTI. Notably, TTI varied by insurance suggesting it may account for a portion of this disparity but did not independently drive survival. Further work is required to identify and develop targeted interventions to address other drivers of reduced survival in those without private insurance. Citation Format: Rebecca AbuAyed, Joshua Schwanke, Brooke Patterson, McKenzie White, Schelomo Marmor, Eric Jensen, Christopher Tignanelli, Emil Lou, Ajay Prakash. Real-world analysis of insurance status and survival in patients with selected GI cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6470.

Conquering chemoresistance in pancreatic cancer: Exploring novel drug therapies and delivery approaches amidst desmoplasia and hypoxia

Pancreatic cancer poses a significant challenge within the field of oncology due to its aggressive behaviour, limited treatment choices, and unfavourable outlook. With a mere 10% survival rate at the 5-year mark, finding effective interventions becomes even more pressing. The intricate relationship between desmoplasia and hypoxia in the tumor microenvironment further complicates matters by promoting resistance to chemotherapy and impeding treatment efficacy. The dense extracellular matrix and cancer-associated fibroblasts characteristic of desmoplasia create a physical and biochemical barrier that impedes drug penetration and fosters an immunosuppressive milieu. Concurrently, hypoxia nurtures aggressive tumor behaviour and resistance to conventional therapies. a comprehensive exploration of emerging medications and innovative drug delivery approaches. Notably, advancements in nanoparticle-based delivery systems, local drug delivery implants, and oxygen-carrying strategies are highlighted for their potential to enhance drug accessibility and therapeutic outcomes. The integration of these strategies with traditional chemotherapies and targeted agents reveals the potential for synergistic effects that amplify treatment responses. These emerging interventions can mitigate desmoplasia and hypoxia-induced barriers, leading to improved drug delivery, treatment efficacy, and patient outcomes in pancreatic cancer. This review article delves into the dynamic landscape of emerging anticancer medications and innovative drug delivery strategies poised to overcome the challenges imposed by desmoplasia and hypoxia in the treatment of pancreatic cancer.

In vitro Cytotoxicity Evaluation of Dandelion Root Ethanol Extract on PANC-1 Cell Line

A challenging diagnosis is the outcome of pancreatic cancer's aggressivity and malignant character. This type of cancer is mostly detected in the metastatic stage. Current treatment options have various side effects, result in the survival rates and quality of life of patients are extremely decreased. Dandelion (Taraxacum officinale (L.) Weber ex F.H. Wigg.) is one of the natural products that has the potential to be therapeutic against a wide range of diseases. This study aimed to evaluate the potential of ethanol extract of dandelion root (DRE) as an alternative anticancer agent. Based on this purpose, milk-rich dandelion roots were collected, cut into small pieces, and then extracted using Soxhlet in the presence of 70% ethanol. The cytotoxic effect of the DRE at certain doses (10, 5, and 2.5 mg/mL) was determined by the Microtetrazolium (MTT) assay for 24, 48, and 72 hours, and half-maximal inhibitory concentration (IC)50 values for these incubation periods were found to be 10 mg/mL, 6.80 mg/mL and 6 mg/mL (p0.001), respectively. As a result, DRE may reduce cell viability when applied to aggressive pancreatic cancer cells and may have the potential to be an alternative anticancer agent. This potential can be clarified with further studies.

Value of the surgical pancreatic duct anatomy and associated outcomes in pancreatic cancer.

Pancreatic cancer recurrence following surgery is a significant challenge, and personalized surgical care is crucial. Topographical variations in pancreatic duct anatomy are frequent but often underestimated. This study aimed to investigate the potential importance of these variations in outcomes and patient survival after Whipple's procedures. Data were collected from 105 patients with confirmed pancreatic head neoplasms who underwent surgery between 2008 and 2020. Radiological measurements of pancreatic duct location were performed, and statistical analysis was carried out using IBM SPSS. Inferior pancreatic duct topography was associated with an increased rate of metastatic spread and tumour recurrence. Additionally, inferior duct topography was associated with reduced overall and recurrence-free survival. Posterior pancreatic duct topography was associated with decreased incidence of perineural sheet infiltration and improved overall survival. These findings suggest that topographical diversity of pancreatic duct location can impact outcomes in Whipple's procedures. Intraoperative review of pancreatic duct location could help surgeons define areas of risk or safety and deliver a personalized surgical approach for patients with beneficial or deleterious anatomical profiles. This study provides valuable information to improve surgical management by identifying high-risk patients and delivering a personalized surgical approach with prognosis stratification.

Machine Learning Links T-cell Function and Spatial Localization to Neoadjuvant Immunotherapy and Clinical Outcome in Pancreatic Cancer.

Tumor molecular data sets are becoming increasingly complex, making it nearly impossible for humans alone to effectively analyze them. Here, we demonstrate the power of using machine learning (ML) to analyze a single-cell, spatial, and highly multiplexed proteomic data set from human pancreatic cancer and reveal underlying biological mechanisms that may contribute to clinical outcomes. We designed a multiplex immunohistochemistry antibody panel to compare T-cell functionality and spatial localization in resected tumors from treatment-naïve patients with localized pancreatic ductal adenocarcinoma (PDAC) with resected tumors from a second cohort of patients treated with neoadjuvant agonistic CD40 (anti-CD40) monoclonal antibody therapy. In total, nearly 2.5 million cells from 306 tissue regions collected from 29 patients across both cohorts were assayed, and over 1,000 tumor microenvironment (TME) features were quantified. We then trained ML models to accurately predict anti-CD40 treatment status and disease-free survival (DFS) following anti-CD40 therapy based on TME features. Through downstream interpretation of the ML models' predictions, we found anti-CD40 therapy reduced canonical aspects of T-cell exhaustion within the TME, as compared with treatment-naïve TMEs. Using automated clustering approaches, we found improved DFS following anti-CD40 therapy correlated with an increased presence of CD44+CD4+ Th1 cells located specifically within cellular neighborhoods characterized by increased T-cell proliferation, antigen experience, and cytotoxicity in immune aggregates. Overall, our results demonstrate the utility of ML in molecular cancer immunology applications, highlight the impact of anti-CD40 therapy on T cells within the TME, and identify potential candidate biomarkers of DFS for anti-CD40-treated patients with PDAC.

Germline mutations of homologous recombination genes and clinical outcomes in pancreatic cancer: a multicenter study in Taiwan

BackgroundCancer susceptibility germline mutations are associated with pancreatic ductal adenocarcinoma (PDAC). However, the hereditary status of PDAC and its impact on survival is largely unknown in the Asian population.MethodsExome sequencing was performed on 527 blood samples from PDAC individuals and analyzed for mutations in 80 oncogenic genes. Pathogenic and likely pathogenic (P/LP) germline variants were diagnosed according to the ACMG variant classification categories. The association between germline homologous recombination gene mutations (gHRmut, including BAP1, BRCA1, BRCA2, PALB2, ATM, BLM, BRIP1, CHEK2, NBN, MUTYH, FANCA and FANCC) and the treatment outcomes was explored in patients with stage III/IV diseases treated with first-line (1L) platinum-based versus platinum-free chemotherapy.ResultsOverall, 104 of 527 (19.7%) patients carried germline P/LP variants. The most common mutated genes were BRCA2 (3.60%), followed by ATR (2.66%) and ATM (1.9%). After a median follow-up duration of 38.3-months (95% confidence interval, 95% CI 35.0–43.7), the median overall survival (OS) was not significantly different among patients with gHRmut, non-HR germline mutations, or no mutation (P = 0.43). Among the 320 patients with stage III/IV disease who received 1L combination chemotherapy, 32 (10%) had gHRmut. Of them, patients receiving 1L platinum-based chemotherapy exhibited a significantly longer median OS compared to those with platinum-free chemotherapy, 26.1 months (95% CI 12.7–33.7) versus 9.6 months (95% CI 5.9–17.6), P = 0.001. However, the median OS of patients without gHRmut was 14.5 months (95% CI 13.2–16.9) and 12.6 months (95% CI 10.8–14.7) for patients receiving 1L platinum-based and platinum-free chemotherapy, respectively (P = 0.22). These results were consistent after adjusting for potential confounding factors including age, tumor stage, performance status, and baseline CA 19.9 in the multivariate Cox regression analysis.ConclusionsOur study showed that nearly 20% of Taiwanese PDAC patients carried germline P/LP variants. The longer survival observed in gHRmut patients treated with 1L platinum-based chemotherapy highlights the importance of germline testing for all patients with advanced PDAC at diagnosis.

An alternative splicing signature defines the basal-like phenotype and predicts worse clinical outcome in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is characterized by extremely poor prognosis. PDAC presents with molecularly distinct subtypes, with the basal-like one being associated with enhanced chemoresistance. Splicing dysregulation contributes to PDAC; however, its involvement in subtype specification remains elusive. Herein, we uncover a subtype-specific splicing signature associated with prognosis in PDAC and the splicing factor Quaking (QKI) as a determinant of the basal-like signature. Single-cell sequencing analyses highlight QKI as a marker of the basal-like phenotype. QKI represses splicing events associated with the classical subtype while promoting basal-like events associated with shorter survival. QKI favors a plastic, quasi-mesenchymal phenotype that supports migration and chemoresistance in PDAC organoids and cell lines, and its expression is elevated in high-grade primary tumors and metastatic lesions. These studies identify a splicing signature that defines PDAC subtypes and indicate that QKI promotes an undifferentiated, plastic phenotype, which renders PDAC cells chemoresistant and adaptable to environmental changes.

Artificial intelligence uses multi-omic data to predict pancreatic cancer outcomes.

Artificial intelligence uses multi-omic data to predict pancreatic cancer outcomes.

Assessing disparities in pancreatic cancer outcomes in African Americans.

612 Background: Pancreatic Adenocarcinoma (PA) is a leading cause of cancer-related death across the world, with poorer outcomes noted in minority populations. The observed variation in outcomes has been attributed to delayed diagnosis, barriers to optimal treatment and health care related disparities. We evaluated the impact of race on clinical presentation and outcomes in pancreatic cancer at a large academic teaching center. Methods: We performed a retrospective review of patients with pancreatic adenocarcinoma diagnosed between January 2016 to December 2021. The demographic characteristics (age, tobacco use, alcohol use, BMI); comorbidities (diabetes, acute/chronic pancreatitis); pathology, treatment (chemotherapy regimen, radiation, surgery) and recurrence free survival (RFS) and overall survival based on race were analyzed. Results: The cohort (N=947) consisted of 147 (16%) African Americans (AA) and 775 (82%) Non-Hispanic Whites (NHW). The mean age at diagnosis was 68 years (±10) among AA and 70 years (±11) in NHW. Thirty-seven (26%) of AA and 104 (14%) of NHW were current smokers; 46 (33%) of AA and 323 (45%) of NHW consumed alcohol regularly. Among AA, 32 (22%) were obese (BMI&gt;30), compared to 194 (25%) in NHW. Other comorbidities included diabetes (35% in AA vs. 32% in NHW) and acute/chronic pancreatitis (11% among AA vs. 9% among NHW). Eighteen percent (18%) of AA and 17% of NHW had stage II disease, 16% and 12% had stage III and 48% in both had stage IV disease respectively. The treatment modality consisted of chemotherapy (63% in AA vs. 66% in NHW), surgery (25% in AA vs. 26% in NHW) and radiation (10% in AA vs. 12% in NHW). The median time to treatment initiation was 30 (17, 41) months for AA and 26 (16, 40) months for NHW. On univariate analysis, AA race was associated with younger age at diagnosis (p 0.043), higher current tobacco use (p 0.001), lower alcohol use (p 0.012), lower rates of obesity (p 0.024) and higher rate of acute pancreatitis (p 0.037) in pancreatic cancer. On multivariate analysis, race was not associated with difference in recurrence free survival (12 months in AA vs. 14 months in NHW; p 0.96) when adjusted for age, sex, alcohol use, tobacco use, cancer stage and chemotherapy. High mean age, clinical stage II, III and IV, current alcohol use, underweight and BMI&gt;30 and cerebrovascular accident as a comorbidity was associated with worse overall survival when adjusted for other variables. Conclusions: Our study revealed that pancreatic cancer in AA was diagnosed at a younger age, associated with active smoking and pancreatitis. We observe there was no difference in treatment initiation among AA and NHW. There was no significant difference in recurrence free survival and overall survival compared to NHW when adjusted for other variables. Future studies incorporating germline mutations, novel biomarkers are needed to determine impact of racial health disparities on outcomes in pancreatic cancer.

Socioeconomic variables in the National Cancer Database: Utilization and impact of income and education in survival models for patients with resected pancreas cancer.

607 Background: The National Cancer Database (NCDB) is commonly used for analyzing survival outcomes in pancreatic cancer and has a robust number of patient-specific socioeconomic variables. Although these aggregated variables are commonly collected, their utility and impact on survival has infrequently been assessed. We aim to assess the distribution of income and education variables on their impact on survival models for patients who underwent resection for pancreatic ductal adenocarcinoma (PDAC). Methods: Patients undergoing definitive surgery for PDAC between 2004-2020 were identified from the NCDB. Variables of interest were income and education according to the patient’s ZIP code of residence. Pearson and Spearman correlation was assessed. Overall survival (OS) was calculated using Kaplan Meier method. The effects of income and education was calculated using Cox proportional Hazard (PH) models. Results: 69,362 patients met inclusion criteria. Median age was 66 (IQR 59-73), with 48.9% female. The correlation coefficient between income and education based on the 2020 American Community Survey data was 0.48 (p&lt;0.01). Median OS from the time of diagnosis was 21 months. The 5-year OS was 19.4 and 22.7 months for groups with lowest and highest education (p&lt;0.01). Group with missing education has a 5-year OS of 22.4 month, comparable to the group with highest education (p=0.82). The 5-year OS based on income quartiles was 18.7 and 22.5 months for the Q1 and Q4 (p&lt;0.01). Group with missing income has a 5-year OS of 22.4 month, similar to the highest income group (p=0.85). When including combinations of income, education and their interaction, the concordance of Cox models was changed by less than 0.002. Conclusions: For patients who underwent definitive surgery for PDAC, the income and education variables are only mildly correlated, and their inclusion do not have significant impact on OS models. Investigators should reconsider the utility of the aggregate NCDB measures, as they many not fully elucidate income and education disparities and impact on survival. [Table: see text]

Advanced pancreatic cancer outcomes and the impact of COVID-19 pandemic: The experience of an academic cancer center.

626 Background: The COVID-19 pandemic increased all-cause mortality and disrupted healthcare delivery in the United States. Interruptions in cancer screening and surveillance because of the pandemic resulted in delayed diagnosis, diagnosis at later stages, and worse cancer-related outcomes. However, the effect of COVID-19 on pancreatic cancer outcomes has not been reported. This study aimed to investigate this question. Methods: We studied consecutive patients with unresectable and metastatic pancreatic cancer treated at the University of Cincinnati Cancer Center. Patients were divided into 2 cohorts: from January 2018 to December 2019 (pre-COVID) and from January of 2020 to December of 2021 (during-COVID). Descriptive data on patient characteristics, ECOG performance status (PS), laboratory values, therapies, and mortality were obtained by pre- and during-COVID. The categorical variables were compared using the Pearson Chi-square test for contingency tables (or Fisher’s exact test when the expected frequency within any cell was less than 5 in the contingency table), and the t-test or ANOVA was used for continuous variables. For overall survival time, the Kaplan-Meier curves were compared between pre- and during-COVID using log rank test. We fitted univariable Cox proportional-hazards model for each interest variable, and the multivariable Cox models, which includes only significant variables. Results: There were 81 and 64 patients in the pre- and during-COVID cohorts, respectively. Patients diagnosed during COVID were more likely to be female, have better PS, have higher proportion of alcohol use, and were more likely to receive 5-FU-based (compared with gemcitabine-based) chemotherapy upfront. There was no overall survival difference between the two cohorts. A Cox proportional hazards model showed that PS at diagnosis, history of chronic pancreatitis, any chemotherapy compared to no chemotherapy, serum albumin prior to initial chemotherapy, and body mass index at time of diagnosis were associated with survival. Conclusions: We observed no difference in overall survival in patients diagnosed with advanced stage pancreatic cancer during the first two years of the COVID-19 pandemic compared with the two prior years. While some differences were observed between patient groups and treatment selection before and during the pandemic, a concerted effort to maintain cancer care appears to have minimized the impact of the pandemic. Further analyses on patients undergoing treatment are being conducted.

Pancreatic cancer progression and mortality predicted by depression and anxiety: a systematic review and meta-analysis protocol.

Although the relationship between psychological factors and pancreatic cancer outcomes has been widely discussed, controversy remains. We will for the first time systematically summarize the literature to explore the correlation of anxiety and depression to the prognosis of patients with pancreatic cancer. The findings will fill existing research gaps, informing healthcare providers about better psychological care and medical treatment. The following databases will be retrieved from their inception to July 2023: Cochrane Library, MEDLINE (PubMed), Web of Science, EMBASE, and four Chinese databases (Chinese National Knowledge Infrastructure, Wanfang Database, Chinese Biomedical Literature Database, and Chongqing VIP Chinese Science and Technology Periodical Database). The World Health Organization Clinical Trials Registry, Chinese Clinical Registry, and ClinicalTrials.gov will be searched to identify other related studies. A manual search will be performed to identify missing eligible studies based on the reference list of selected articles. The search will focus on studies published in Chinese or English. To assess the risk of bias in the selected articles, Newcastle-Ottawa Quality Assessment Scale (NOS) will be used for the cohort study. Funnel plots and Egger's test will be used to assess whether publication bias exists. Moreover, the Grading of Recommendations Assessment Development and Evaluation (GRADE) will be utilized to analyze the credibility of the results from selected articles. Two independent evaluators will implement the study selection and data extraction, as well as evaluate the risk of bias and evidence quality. Data will be analyzed using Stata 16.0. Trial registration: PROSPERO registration number is CRD42022366232.

Survival outcomes in intraductal papillary mucinous neoplasm-derived pancreatic cancer differs from PanIN-derived pancreatic cancer: an international propensity-matched analysis

Survival outcomes in intraductal papillary mucinous neoplasm-derived pancreatic cancer differs from PanIN-derived pancreatic cancer: an international propensity-matched analysis

Host phenotype profiling predicts outcomes in neoadjuvant pancreatic cancer

Host phenotype profiling predicts outcomes in neoadjuvant pancreatic cancer

Long-term outcomes for resectable pancreatic head cancer in patients >70 years old

Long-term outcomes for resectable pancreatic head cancer in patients >70 years old