Olaparib not cost-effective as maintenance therapy for platinum-sensitive, BRCA1/2 germline-mutated metastatic pancreatic cancer.

OBJECTIVE: To assess the cost-effectiveness and budget impact of olaparib as a maintenance therapy in platinum-responsive, metastatic pancreatic cancer patients harboring a germline BRCA1/2 mutation, using the Swiss context as a model. METHODS: Based on data from the POLO trial, published literature and local cost data, we developed a partitioned survival model of olaparib maintenance including full costs for BRCA1/2 germline testing compared to FOLFIRI maintenance chemotherapy and watch-and-wait. We calculated the incremental cost-effectiveness ratio (ICER) for the base case and several scenario analyses and estimated 5-year budget impact. RESULTS: Comparing olaparib with watch-and wait and maintenance chemotherapy resulted in incremental cost-effectiveness ratios of CHF 2,711,716 and CHF 2,217,083 per QALY gained, respectively. The 5-year costs for the olaparib strategy in Switzerland would be CHF 22.4 million, of which CHF 11.4 million would be accounted for by germline BRCA1/2 screening of the potentially eligible population. This would amount to a budget impact of CHF 15.4 million (USD 16.9 million) versus watch-and-wait. CONCLUSIONS: Olaparib is not a cost-effective maintenance treatment option. Companion diagnostics are an equally important cost driver as the drug itself.

Predicting the Risk of Morbidity by GLIM-Based Nutritional Assessment and Body Composition Analysis in Oncologic Abdominal Surgery in the Context of Enhanced Recovery Programs : The PHase Angle Value in Abdominal Surgery (PHAVAS) Study.

BACKGROUND: Preoperative nutritional status and body structure affect short-term prognosis in patients undergoing major oncologic surgery. Bioimpedance vectorial analysis (BIVA) is a reliable tool to assess body composition. Low BIVA-derived phase angle (PA) indicates a decline of cell membrane integrity and function. The aim was to study the association between perioperative PA variations and postoperative morbidity following major oncologic upper-GI surgery. PATIENTS AND METHODS: Between 2019 and 2022 we prospectively performed BIVA in patients undergoing surgical resection for pancreatic, hepatic, and gastric malignancies on the day before surgery and on postoperative day (POD) 1. Malnutrition was defined as per the Global Leadership Initiative on Malnutrition criteria. The PA variation (ΔPA) between POD1 and preoperatively was considered as a marker for morbidity. Uni and multivariable logistic regression models were applied. RESULTS: Overall, 542 patients with a mean age of 64.6 years were analyzed, 279 (51.5%) underwent pancreatic, 201 (37.1%) underwent hepatobiliary, and 62 (11.4%) underwent gastric resections. The prevalence of preoperative malnutrition was 16.6%. The overall morbidity rate was 53.3%, 59% in those with ΔPA < -0.5 versus 46% when ΔPA ≥ -0.5. Age [odds ratio (OR) 1.11; 95% confidence interval (CI) (1.00; 1.22)], pancreatic resections [OR 2.27; 95% CI (1.24; 4.18)], estimated blood loss (OR 1.20; 95% CI (1.03; 1.39)], malnutrition [OR 1.77; 95% CI (1.27; 2.45)], and ΔPA [OR 1.59; 95% CI (1.54; 1.65)] were independently associated with postoperative complications in the multivariate analysis. CONCLUSIONS: Patients with preoperative malnutrition were significantly more likely to develop postoperative morbidity. Moreover, a decrease in PA on POD1 was independently associated with a 13% increase in the absolute risk of complications. Whether proactive interventions may reduce the downward shift of PA and the complication rate need further investigation.

Efficient Assessment of Tumor Vascular Shutdown by Photodynamic Therapy on Orthotopic Pancreatic Cancer Using High-Speed Wide-Field Waterproof Galvanometer Scanner Photoacoustic Microscopy.

To identify the vascular alteration by photodynamic therapy (PDT), the utilization of high-resolution, high-speed, and wide-field photoacoustic microscopy (PAM) has gained enormous interest. The rapid changes in vasculature during PDT treatment and monitoring of tumor tissue activation in the orthotopic pancreatic cancer model have received limited attention in previous studies. Here, a fully two-axes waterproof galvanometer scanner-based photoacoustic microscopy (WGS-PAM) system was developed for in vivo monitoring of dynamic variations in micro blood vessels due to PDT in an orthotopic pancreatic cancer mouse model. The photosensitizer (PS), Chlorin e6 (Ce6), was utilized to activate antitumor reactions in response to the irradiation of a 660 nm light source. Microvasculatures of angiogenesis tissue were visualized on a 40 mm2 area using the WGS-PAM system at 30 min intervals for 3 h after the PDT treatment. The decline in vascular intensity was observed at 24.5% along with a 32.4% reduction of the vascular density at 3 h post-PDT by the analysis of PAM images. The anti-vascularization effect was also identified with fluorescent imaging. Moreover, Ce6-PDT increased apoptotic and necrotic markers while decreasing vascular endothelial growth factor (VEGF) expression in MIA PaCa-2 and BxPC-3 pancreatic cancer cell lines. The approach of the WGS-PAM system shows the potential to investigate PDT effects on the mechanism of angiographic dynamics with high-resolution wide-field imaging modalities.

Postoperative outcomes and costs of laparoscopic versus robotic distal pancreatectomy: a propensity-matched analysis.

BACKGROUND: Minimally invasive distal pancreatectomy (MIDP) has established advantages over the open approach. The costs associated with robotic DP (RDP) versus laparoscopic DP (LDP) make the robotic approach controversial. We sought to compare outcomes and cost of LDP and RDP using propensity matching analysis at our institution. METHODS: Patients undergoing LDP or RDP between 2000 and 2021 were retrospectively identified. Patients were optimally matched using age, gender, American Society of Anesthesiologists status, body mass index, and tumor size. Between-group differences were analyzed using the Wilcoxon signed-rank test for continuous data, and the McNemar's test for categorical data. Outcomes included operative duration, conversion to open surgery, postoperative length of stay, pancreatic fistula rate, pseudocyst requiring intervention, and costs. RESULTS: 298 patients underwent MIDP, 180 (60%) were laparoscopic and 118 (40%) were robotic. All RDPs were matched 1:1 to a laparoscopic case with absolute standardized mean differences for all matching covariates below 0.10, except for tumor type (0.16). RDP had longer operative times (268 vs 178 min, p < 0.01), shorter length of stay (2 vs 4 days, p < 0.01), fewer biochemical pancreatic leaks (11.9% vs 34.7%, p < 0.01), and fewer interventional radiological drainage (0% vs 5.9%, p = 0.01). The number of pancreatic fistulas (11.9% vs 5.1%, p = 0.12), collections requiring antibiotics or intervention (11.9% vs 5.1%, p = 0.12), and conversion rates (3.4% vs 5.1%, p = 0.72) were comparable between the two groups. The total direct index admission costs for RDP were 1.01 times higher than for LDP for FY16-19 (p = 0.372), and 1.33 times higher for FY20-22 (p = 0.031). CONCLUSIONS: Although RDP required longer operative times than LDP, postoperative stays were shorter. The procedure cost of RDP was modestly more expensive than LDP, though this was partially offset by reduced hospital stay and reintervention rate.

The impacts of exposure to risk factors during youth on the increasing global trend of early-onset pancreatic cancer.

OBJECTIVES: An increasing trend of pancreatic cancer in young adults has emerged in some countries. This study aimed to investigate global trends of pancreatic cancer in young adults and explore the impact of exposure to risk factors on pancreatic cancer incidence during youth. METHODS: Global and national data on pancreatic cancer incidence, disability-adjusted life-years, attributive mortality, and summary exposure values of risk factors were retrieved from the Global Burden of Disease 2019. The average annual percent change (AAPC) of incidence and mortality was calculated. Additionally, generalized additive models were applied to explore the non-linear associations between the levels and changes in the Human Development Index and AAPC. RESULTS: Global pancreatic cancer incidence increased during various periods from 1990 to 2019, particularly in adults aged <45 years from 2010 to 2019, at an average annual increase rate of 0.7% (95% confidence interval: 0.4-1.0%). The AAPC of early-onset pancreatic cancer incidence from 2010 to 2019 was negatively correlated with Human Development Index levels in both 2010 and 2019 but positively correlated with Human Development Index acceleration. Significant increases in early-onset pancreatic cancer incidence were observed over this period in 32 of 88 countries, primarily in South America, North America, Oceania, and Africa. Early-onset pancreatic cancer mortality attributed to high body mass index and fasting plasma glucose increased, while that attributed to tobacco use declined. CONCLUSIONS: An increasing trend has emerged in the global incidence and burden of early-onset pancreatic cancer over the last few decades. This rise may partly be attributed to global epidemics of high body mass index and fasting plasma glucose.

Epidemiology and Socioeconomic Impact of Pancreatic Cancer: An Analysis of the Global Burden of Disease Study 1990-2019.

INTRODUCTION: The aim of this study is to estimate the global burden of pancreatic cancer from 1990 to 2019. METHODS: We reconstructed the Global Burden of Diseases (GBD) study results for pancreatic cancer across 204 countries and territories. Our study generated estimates for key disease burden indicators, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs), and cost. Linear regression analysis of the natural logarithm of age-standardized outcomes was used to calculate annual percent change. RESULTS: In 2019, there were a total of 530,296 incident and 442,101 prevalent cases of pancreatic cancer, resulting in 531,107 deaths and 11.5 million DALYs lost. The age-standardized incidence and prevalence of pancreatic cancer has increased from 5.22 (95% CI 4.97-5.40) to 6.57 (CI 6.00-7.09) per 100,000 people per year, and 4.1 (95% CI 3.95-4.26) to 5.4 (CI 4.96-5.87), respectively. This equated to 10 million (95% CI 9.5 to 10.4 million) incident cases of pancreatic cancer. The number of DALYs lost as a result of pancreatic cancer was 225 million years (95% CI 216-234 million years). Mortality from pancreatic cancer increased over the study period from 3.7 (95% CI 3.54-3.83) to 6.9 (95% CI 6.36-7.32). Incidence, prevalence, DALYs, and mortality were higher in countries with a higher socio-demographic index. CONCLUSIONS: Pancreatic cancer is rising around the world and is associated with a high economic burden. Programs aimed at reducing modifiable risk factors are needed.

Simulating the healthcare workforce impact and capacity for pancreatic cancer care in Victoria: a model-based analysis.

BACKGROUND: The incidence of pancreatic cancer is rising. With improvements in knowledge for screening and early detection, earlier detection of pancreatic cancer will continue to be more common. To support workforce planning, our aim is to perform a model-based analysis that simulates the potential impact on the healthcare workforce, assuming an earlier diagnosis of pancreatic cancer. METHODS: We developed a simulation model to estimate the demand (i.e. new cases of pancreatic cancer) and supply (i.e. the healthcare workforce including general surgeons, medical oncologists, radiation oncologists, pain medicine physicians, and palliative care physicians) between 2023 and 2027 in Victoria, Australia. The model compares the current scenario to one in which pancreatic cancer is diagnosed at an earlier stage. The incidence of pancreatic cancer in Victoria, five-year survival rates, and Victoria's population size were obtained from Victorian Cancer Registry, Cancer Council NSW, and Australian Bureau of Statistics respectively. The healthcare workforce data were sourced from the Australian Government Department of Health and Aged Care's Health Workforce Data. The model was constructed at the remoteness level. We analysed the new cases and the number of healthcare workforce by profession together to assess the impact on the healthcare workforce. RESULTS: In the status quo, over the next five years, there will be 198 to 220 stages I-II, 297 to 330 stage III, and 495 to 550 stage IV pancreatic cancer cases diagnosed annually, respectively. Assuming 20-70% of the shift towards pancreatic cancer's earlier diagnosis (shifting from stage IV to stages I-II pancreatic cancer within one year), the stages I-II cases could increase to 351 to 390 or 598 to 665 per year. The shift to early diagnosis led to substantial survival gains, translating into an additional 284 or 795 out of 5246 patients with pancreatic cancer remaining alive up to year 5 post-diagnosis. Workforce supply decreases significantly by the remoteness levels, and remote areas face a shortage of key medical professionals registered in delivering pancreatic cancer care, suggesting travel necessities by patients or clinicians. CONCLUSION: Improving the early detection and diagnosis of pancreatic cancer is expected to bring significant survival benefits, although there are workforce distribution imbalances in Victoria that may affect the ability to achieve the anticipated survival gain.

Accessibility to ERCP-performing hospitals among patients with pancreatic cancer living in SEER regions.

BACKGROUND AND AIMS: The two most common interventions used to treat painless jaundice from pancreatic cancer are endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic biliary drainage (PTBD). Our study aimed to characterize the geographic distribution of ERCP-performing hospitals among patients with pancreatic cancer in the United States and the association between geographic accessibility to ERCP-performing hospitals and biliary interventions patients receive. METHODS: This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database for pancreatic cancer from 2005 to 2013. Multilevel models were used to examine the association between accessibility to ERCP hospitals within a 30- and 45-min drive from the patient's residential ZIP Code and the receipt of ERCP treatment. A two-step floating catchment area model was used to calculate the measure of accessibility based on the distribution across SEER regions. RESULTS: 7464 and 782 patients underwent ERCP and PTBD, respectively, over the study period. There were 808 hospitals in which 8246 patients diagnosed with pancreatic cancer in SEER regions from 2005 to 2013 received a procedure. Patients with high accessibility within both 30- and 45-min drive to an ERCP-performing hospital were more likely to receive an ERCP (30-min adjusted odds ratio [aOR]: 1.53, 95% confidence interval [CI]: 1.17-2.01; 45-min aOR: 1.31, 95% CI: 1.01-1.70). Furthermore, in the adjusted model, Black patients (vs. White) and patients with stage IV disease were less likely to receive ERCP than PTBD. CONCLUSIONS: Patients with pancreatic cancer and high accessibility to an ERCP-performing hospital were more likely to receive ERCP. Disparities in the receipt of ERCP persisted for Black patients regardless of their access to ERCP-performing hospitals.

Medicaid Expansion Increases Access for Rural and Impoverished Patients with Pancreatic Ductal Adenocarcinoma in Southern States.

INTRODUCTION: Medicaid expansion (ME) impacted patients when assessed at a national level. However, of the 32 states in which Medicaid expansion occurred, only 3 were Southern states. Whether results apply to Southern states that share similar geopolitical perspectives remains elusive. We aimed to assess the impact of ME on pancreatic ductal adenocarcinoma (PDAC) treatment in eight Southern states in the USA. PATIENTS AND METHODS: We identified uninsured or Medicaid patients (age 40-64 years) diagnosed with PDAC between 2011 and 2018 in Southern states from the North American Association of Central Cancer Registries-Cancer in North America (NAACCR-CiNA) research dataset. Medicaid-expanded states (MES; Louisiana, Kentucky, and Arkansas) were compared with non-MES (NMES; Tennessee, Alabama, Mississippi, Texas, and Oklahoma) using multivariate logistic regression. P < 0.05 was considered statistically significant. RESULTS: Among 3036 patients, MES significantly increased odds of Medicaid insurance by 36%, and increased proportions of insured Black patients by 3.7%, rural patients by 3.8%, and impoverished patients by 18.4%. After adjusting for age, race, rural-urban status, poverty status, and summary stage, the odds of receiving radiation therapy decreased by 26% for each year of expansion in expanded states (P = 0.01). Last, ME did not result in a significant difference between MES and NMES in diagnosing early stage disease (P = 0.98) nor in receipt of chemotherapy or surgery (P = 0.23 and P = 0.63, respectively). CONCLUSIONS: ME in Southern states increased insurance access to traditionally underserved groups. Interestingly, ME decreased the odds of receiving radiation therapy yearly and had no significant impact on receipt of chemotherapy or surgery.

A Randomized Trial of Two Remote Health Care Delivery Models on the Uptake of Genetic Testing and Impact on Patient-Reported Psychological Outcomes in Families With Pancreatic Cancer: The Genetic Education, Risk Assessment, and Testing (GENERATE) Study.

BACKGROUND & AIMS: Genetic testing uptake for cancer susceptibility in family members of patients with cancer is suboptimal. Among relatives of patients with pancreatic ductal adenocarcinoma (PDAC), The GENetic Education, Risk Assessment, and TEsting (GENERATE) study evaluated 2 online genetic education/testing delivery models and their impact on patient-reported psychological outcomes. METHODS: Eligible participants had ≥1 first-degree relative with PDAC, or ≥1 first-/second-degree relative with PDAC with a known pathogenic germline variant in 1 of 13 PDAC predisposition genes. Participants were randomized by family, between May 8, 2019, and June 1, 2021. Arm 1 participants underwent a remote interactive telemedicine session and online genetic education. Arm 2 participants were offered online genetic education only. All participants were offered germline testing. The primary outcome was genetic testing uptake, compared by permutation tests and mixed-effects logistic regression models. We hypothesized that Arm 1 participants would have a higher genetic testing uptake than Arm 2. Validated surveys were administered to assess patient-reported anxiety, depression, and cancer worry at baseline and 3 months postintervention. RESULTS: A total of 424 families were randomized, including 601 participants (n = 296 Arm 1; n = 305 Arm 2), 90% of whom completed genetic testing (Arm 1 [87%]; Arm 2 [93%], P = .014). Arm 1 participants were significantly less likely to complete genetic testing compared with Arm 2 participants (adjusted ratio [Arm1/Arm2] 0.90, 95% confidence interval 0.78-0.98). Among participants who completed patient-reported psychological outcomes questionnaires (Arm 1 [n = 194]; Arm 2 [n = 206]), the intervention did not affect mean anxiety, depression, or cancer worry scores. CONCLUSIONS: Remote genetic education and testing can be a successful and complementary option for delivering genetics care. (Clinicaltrials.gov, number NCT03762590).

Prognostic potential of nutritional risk screening and assessment tools in predicting survival of patients with pancreatic neoplasms: a systematic review.

BACKGROUNDS & AIMS: The nutritional evaluation of pancreatic cancer (PC) patients lacks a gold standard or scientific consensus, we aimed to summarize and systematically evaluate the prognostic value of nutritional screening and assessment tools used for PC patients. METHODS: Relevant studies were retrieved from major databases (PubMed, Embase, Web of Science, Cochrane Library) and searched from January 2010 to December 2023. We performed meta-analyses with STATA 14.0 when three or more studies used the same tool. RESULTS: This analysis included 27 articles involving 6,060 PC patients. According to a meta-analysis of these studies, poor nutritional status evaluated using five nutritional screening tools Prognostic Nutritional Index (PNI), Geriatric Nutritional Risk Index (GNRI), Controlling Nutritional Status Score (CONUT), Nutrition Risk Screening (NRS2002) and Glasgow Prognostic Score (GPS) was associated with all-cause mortality in PC patients. But Modified Glasgow Prognostic Score (mGPS) did not. Of all tools analyzed, CONUT had the maximum HR for mortality (HR = 1.978, 95%CI 1.345-2.907, P = 0.001). CONCLUSION: All-cause mortality in PC patients was predicted by poor nutritional status. CONUT may be the best nutritional assessment tool for PC patients. The clinical application value of Short Form Mini Nutritional Assessment (MNA-SF), Generated Subjective Global Assessment (SGA) and Patient-generated Subjective Global Assessment (PG-SGA) in PC patients need to be confirmed. In order to improve patients' nutritional status and promote their recovery, nutritional screening tools can be used. REGISTRATION: This systematic review was registered at the International Prospective Register of Systematic Reviews (PROSPERO) (number CRD42022376715).

Global burden of pancreatic cancer attributable to metabolic risks from 1990 to 2019, with projections of mortality to 2030.

OBJECTIVE: Metabolic risks play a key role in the progression of pancreatic cancer. This study aimed to present global, regional and national data on mortality and disability-adjusted life-year (DALY) for pancreatic cancer attributable to metabolic risk and to forecast mortality to 2030 using data from the Global Burden of Disease (GBD). METHODS: Data on mortality and DALYs due to pancreatic cancer attributable to metabolic risks were obtained from GBD 2019. Metabolic risks include high fasting plasma glucose (FPG) and high body mass index (BMI). Total numbers and age-standardized rates per 100,000 people for mortality and DALYs were reported by age, sex, region and country/territory from 1990 to 2019. The "Bayes age-period-cohort" method was used for projections of mortality to 2030. RESULTS: Globally, there was a 3.5-fold increase in the number of pancreatic cancer deaths attributable to metabolic risk, from 22,091 in 1990 to 77,215 in 2019. High-income North America and Central Europe had the highest age-standardized mortality rates (ASMRs) of pancreatic cancer attributable to high FPG and high BMI in 2019, respectively. From 1990 to 2019, the global ASMR of pancreatic cancer attributable to high FPG and high BMI increased. Countries with high healthcare access quality had much higher age-standardized DALY rates. In the next 10 years, the ASMR of pancreatic cancer attributable to high FPG and high BMI will continue to increase. CONCLUSION: Pancreatic cancer mortality and DALYs attributable to metabolic factors remain high, particularly in high-income regions or countries. Studies on the metabolic mechanism of pancreatic cancer and effective treatment strategies are needed.

Epidemiology and economic burden of Von Hippel-Lindau Disease-associated central nervous system hemangioblastomas and pancreatic neuroendocrine tumors in the United States.

BACKGROUND: To date, real-world evidence around the clinical and economic burden related to von Hippel-Lindau (VHL) disease is limited. Therefore, this study characterized the prevalence, healthcare resource utilization (HRU), and economic burden of von Hippel-Lindau-associated central nervous system hemangioblastoma (VHL-CNS-Hb) and pancreatic neuroendocrine tumors (VHL-pNET) in the United States (US). METHODS: Patients with VHL-CNS-Hb or VHL-pNET were identified from Optum's de-identified Clinformatics® Data Mart Database (2007-2020) and matched 1:5 to control patients without VHL disease or CNS-Hb/pNET. Prevalence rates of VHL-CNS-Hb and VHL-pNET (standardized by age and sex) in 2019 were estimated. HRU and healthcare costs (2020 US dollars) were compared between the VHL-CNS-Hb/VHL-pNET and control cohorts. RESULTS: In 2019, US prevalence rates of VHL-CNS-Hb and VHL-pNET were estimated to be 1.12 cases per 100,000 (3,678 patients) and 0.12 cases per 100,000 (389 patients), respectively. Patients with VHL-CNS-Hb (N = 220) had more inpatient, outpatient, and emergency department visits and $49,645 higher annual healthcare costs than controls (N = 1,100). Patients with VHL-pNET (N = 20) had more inpatient and outpatient visits and $56,580 higher annual healthcare costs than controls (N = 100). Costs associated with surgical removal of CNS-Hb and pNET were particularly high. CONCLUSIONS: In this retrospective, claims-based study, both VHL-CNS-Hb and VHL-pNET were associated with substantial HRU and healthcare costs, particularly tumor reduction surgery-related costs. These findings provide important insight for healthcare payers regarding the expected real-world costs that enrollees with VHL-CNS-Hb and VHL-pNET may incur over the course of their disease.

Artificial intelligence for assessment of vascular involvement and tumor resectability on CT in patients with pancreatic cancer.

OBJECTIVE: This study aimed to develop and evaluate an automatic model using artificial intelligence (AI) for quantifying vascular involvement and classifying tumor resectability stage in patients with pancreatic ductal adenocarcinoma (PDAC), primarily to support radiologists in referral centers. Resectability of PDAC is determined by the degree of vascular involvement on computed tomography scans (CTs), which is associated with considerable inter-observer variability. METHODS: We developed a semisupervised machine learning segmentation model to segment the PDAC and surrounding vasculature using 613 CTs of 467 patients with pancreatic tumors and 50 control patients. After segmenting the relevant structures, our model quantifies vascular involvement by measuring the degree of the vessel wall that is in contact with the tumor using AI-segmented CTs. Based on these measurements, the model classifies the resectability stage using the Dutch Pancreatic Cancer Group criteria as either resectable, borderline resectable, or locally advanced (LA). RESULTS: We evaluated the performance of the model using a test set containing 60 CTs from 60 patients, consisting of 20 resectable, 20 borderline resectable, and 20 locally advanced cases, by comparing the automated analysis obtained from the model to expert visual vascular involvement assessments. The model concurred with the radiologists on 227/300 (76%) vessels for determining vascular involvement. The model's resectability classification agreed with the radiologists on 17/20 (85%) resectable, 16/20 (80%) for borderline resectable, and 15/20 (75%) for locally advanced cases. CONCLUSIONS: This study demonstrates that an AI model may allow automatic quantification of vascular involvement and classification of resectability for PDAC. RELEVANCE STATEMENT: This AI model enables automated vascular involvement quantification and resectability classification for pancreatic cancer, aiding radiologists in treatment decisions, and potentially improving patient outcomes. KEY POINTS: • High inter-observer variability exists in determining vascular involvement and resectability for PDAC. • Artificial intelligence accurately quantifies vascular involvement and classifies resectability for PDAC. • Artificial intelligence can aid radiologists by automating vascular involvement and resectability assessments.

CKS1B as a potential target for prognostic assessment and intervention in pancreatic cancer and its role in abnormal proliferation and cellular phenotype through mediation of cell cycle signaling pathways.

OBJECTIVES: To investigate the role of cell cycle protein-dependent kinase regulatory subunit 1B (CKS1B) in driving the aggressive and rapid proliferation observed in pancreatic cancer. METHODS: A comprehensive analysis was carried out using raw mRNA information and data from 2 databases: the cancer genome atlas and gene expression omnibus. The differential expression of CKS1B at the mRNA and tissue levels in cancer and adjacent paracancerous tissues were assessed. Additionally, the relationship of CKS1B expression and overall survival (OS) rate was investigated using Kaplan-Meier survival curves. Potential molecular mechanisms by which CKS1B may influence the biological characteristics of pancreatic cancer were explored using resources available within the encyclopedia of RNA interactomes database. RESULTS: The CKS1B exhibited significant differential expression at the mRNA as well as protein levels. A correlation with statistical significance between CKS1B expression and N stage, age, and alcohol consumption was observed. Notably, high CKS1B expression was determined as a predictive factor for worse OS. Furthermore, the analysis revealed a potential synergistic role between CKS1B and the molecule PKMYT1, which could impact the ATR-Chk1-Cdc25 signaling pathway and disrupt the G2/M checkpoint within the cell cycle, ultimately promoting abnormal tumor proliferation. CONCLUSION: The CKS1B may serve as a novel potential prognostic factor in pancreatic cancer and is involved in the abnormal proliferation biology phenotype by mediating cell cycle signaling pathways.

Short-term serial circulating tumor DNA assessment predicts therapeutic efficacy for patients with advanced pancreatic cancer.

PURPOSE: We investigated the potential clinical utility of short-term serial KRAS-mutated circulating cell-free tumor DNA (ctDNA) assessment for predicting therapeutic response in patients undergoing first-line chemotherapy for advanced pancreatic cancer. METHODS: We collected 144 blood samples from 18 patients with locally advanced or metastatic cancer that were undergoing initial first-line chemotherapy of gemcitabine plus nab-paclitaxel (GEM plus nab-PTX). Analysis of KRAS-mutated ctDNA was quantified by digital droplet polymerase chain reaction (ddPCR) as mutant allele frequency (MAF). This study investigated pretreatment KRAS-mutated ctDNA status and ctDNA kinetics every few days (days 1, 3, 5 and 7) after initiation of chemotherapy and their potential as predictive indicators. RESULTS: Of the 18 enrolled patients, an increase in KRAS-mutated ctDNA MAF values from day 0-7 after initiation of chemotherapy was significantly associated with disease progression (P < 0.001). Meanwhile, positive pretreatment ctDNA status (MAF ≥ 0.02%) (P = 0.585) and carbohydrate antigen 19-9 (CA19-9) values above the median (P = 0.266) were not associated with disease progression. In univariate analysis, this short-term increase in ctDNA MAF values (day 0-7) was found to be associated with significantly shorter progression free survival (PFS) (hazard ration [HR], 24.234; range, (2.761-212.686); P = 0.0002). CONCLUSION: This short-term ctDNA kinetics assessment may provide predictive information to reflect real-time therapeutic response and lead to effective refinement of regimen in patients with advanced pancreatic cancer undergoing systemic chemotherapy.

Global, regional, and national burdens of early onset pancreatic cancer in adolescents and adults aged 15-49 years from 1990 to 2019 based on the Global Burden of Disease Study 2019: a cross-sectional study.

BACKGROUND: Early-onset pancreatic cancer (EOPC) in younger populations (age ≤50 years) is likely to be a more aggressive phenotype characterized by poor differentiation. The emerging analysis of the global burden of EOPC is limited and outdated. AIM: To systematically investigate the burden and trend of EOPC based on global populations. METHODS: In this systematic analysis based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, the authors present the number of cases, age-standardized rates (ASRs) per 100 000 population, and risk factors for 204 countries and territories. The average annual percentage changes (AAPCs) for the incidence, mortality, and disability-adjusted life-years (DALYs) of EOPC were calculated using joinpoint regression analysis. RESULTS: According to the GBD 2019 estimates, there were 36 852 new cases of EOPC and 32 004 related deaths. East Asia had the highest number of cases, with 11 401 incidences and 10 149 deaths. The ASRs were 0.94 per 100 000 individuals for incidence and 0.81 per 100 000 for mortality. From 1990 to 2019, the age-standardized incidence increased by 46.9%, mortality increased by 44.6%, and DALYs increased by 41.9% globally. In trend analysis, the global incidence (AAPC, 1.26), mortality (AAPC, 1.24), and DALYs (AAPC, 1.25) of EOPC showed an increasing pattern. The ASRs of incidence, mortality, and DALYs of EOPC in Africa, America, and Asia exhibited a continuous upward trend, while the trend in Europe was fluctuating. Asian males exhibited the fastest growth in incidence (AAPC, 2.15) and mortality (AAPC, 2.13), whereas males in the Americas experienced the slowest increase in new cases (AAPC, 0.72) and deaths (AAPC, 0.67). A certain proportion of EOPC DALYs were attributable to known risk factors: tobacco smoking (13.3%), high BMI, 5.6%, and high fasting plasma glucose 3.2%. Integrating the socio-demographic index (SDI), ASRs of incidence and mortality initially increased with rising SDI, reaching a peak in central Europe (1.5 per 100 000

Magnetic Resonance Imaging-Based Assessment of Pancreatic Fat Strongly Correlates With Histology-Based Assessment of Pancreas Composition.

OBJECTIVE: The aim of the study is to assess the relationship between magnetic resonance imaging (MRI)-based estimation of pancreatic fat and histology-based measurement of pancreatic composition. MATERIALS AND METHODS: In this retrospective study, MRI was used to noninvasively estimate pancreatic fat content in preoperative images from high-risk individuals and disease controls having normal pancreata. A deep learning algorithm was used to label 11 tissue components at micron resolution in subsequent pancreatectomy histology. A linear model was used to determine correlation between histologic tissue composition and MRI fat estimation. RESULTS: Twenty-seven patients (mean age 64.0 ± 12.0 years [standard deviation], 15 women) were evaluated. The fat content measured by MRI ranged from 0% to 36.9%. Intrapancreatic histologic tissue fat content ranged from 0.8% to 38.3%. MRI pancreatic fat estimation positively correlated with microanatomical composition of fat (r = 0.90, 0.83 to 0.95], P < 0.001); as well as with pancreatic cancer precursor ( r = 0.65, P < 0.001); and collagen ( r = 0.46, P < 0.001) content, and negatively correlated with pancreatic acinar ( r = -0.85, P < 0.001) content. CONCLUSIONS: Pancreatic fat content, measurable by MRI, correlates to acinar content, stromal content (fibrosis), and presence of neoplastic precursors of cancer.