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Showing 10 of 107964 citations.

Functional role of GLI2 in cancer-associated fibroblasts for modulation of the fibrotic tumor microenvironment within pancreatic cancer.
Kwon, John , Vera, Renzo E., Fernadez-Barrena, Maite G., Falero, Jose M. , Chaparro, Roberto G., Ross, Matthew D., Törüner, Murat , Almada, Luciana L. , Fernández-Zapico, Martín E. , Chaparro, Roberto G., Ross, Matthew D., Toruner, Merih Deniz , Toruner, Murat, Tolosa, Ezequiel J. , Huang, Huocong , Brekken, Rolf A.

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 4155-4155

10.1200/jco.2025.43.16_suppl.4155 Get It

4155 Background: The tumor microenvironment (TME) that surrounds pancreatic ductal adenocarcinoma (PDAC) is a multi-faceted and dynamic ecosystem in which stromal fibroblasts communicate with cancer cells to mediate tumor growth, metastasis, and chemotherapy resistance. It is well recognized that both cancer-associated fibroblasts (CAFs) and its non-cellular, fibrotic components within the TME can foster a protumorigenic environment for PDAC. However, we still lack a comprehensive understanding of the precise mechanisms in which this dense, fibrotic matrix can help drive malignant behaviors. Here, we reveal a novel mechanism in which the zinc-finger transcription factor GLI2 regulates type 1 collagen expression within CAFs and how the soluble variant of this collagen promotes irinotecan chemoresistance. Methods: We leveraged transcriptomic data from The Cancer Genome Atlas, International Cancer Genome Consortium, and Clinical Proteomic Tumor Analysis Consortium to evaluate GLI2 expression and stromal content of human PDAC tumors through bulk RNA-sequencing deconvolution. Using single-nucleus RNA sequencing of human PDAC tumors, we validated the association of GLI2 expression and stromal matrix constituents in CAFs. Chromatin immunoprecipitation assays in human CAFs confirmed GLI2 binding at the COL1A1 promoter. Through RNAi-based inactivation of GLI2, we determined how loss of GLI2 impacts regulation of type 1 collagen. Additionally, we conducted MTT assays to assess tumor viability in response to irinotecan treatment. Results: Transcriptomic analysis revealed that GLI2 is highly enriched in CAFs and strongly correlated with stromal fibrosis compared to other non-tumor cell constituents within the TME. We have shown that GLI2 directly binds to the promoter of COL1A1, a key component of type 1 collagen, in CAFs and regulates its transcription in a manner dependent on TGFβ1 signaling. Interestingly, PDAC tumors exposed to type 1 collagen show increased expression of pro-tumorigenic pathways involved in inflammation, EGR signaling, cytokine-receptor interactions, and irinotecan resistance. We further validate that human PDAC cells pre-treated with collagen can confer chemoresistance to irinotecan with viability assays. Conclusions: Taken together, our study demonstrates a novel mechanism in which GLI2 regulates the secretion of collagen within CAFs, which in turn can enable PDAC to acquire resistance to standard-of-care treatments. These findings highlight not only the oncogenic functions for CAFs and their fibrotic secretome, but also open new avenues in which therapeutic targeting of the TME may provide clinical benefit for PDAC patients.
Preliminary results from the randomized phase 2 study (1801 part 3B) of elraglusib in combination with gemcitabine/nab-paclitaxel (GnP) versus GnP alone in patients (pts) with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC).
Shroff, Rachna T. , Carneiro, Benedito A. , Sahai, Vaibhav , Ploquin, Anne , Hiret, Sandrine , Percent, Ivor , Pernot, Simon , Kavan, Petr , Mulcahy, Mary F. , Mazar, Andrew P. , Fine, Gil D., Sahai, Vaibhav , Mahalingam, Devalingam , Ji, Yan , Coveler, Andrew L. , Cervantes, Andrés , LoConte, Noelle K. , Lopez, Charles D. , Carr, Ryan M , Giles, Francis Joseph , Bekaii‐Saab, Tanios

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 4006-4006

10.1200/jco.2025.43.16_suppl.4006 Get It

4006 Background: Elraglusib (9-ING-41) is a first-in-class inhibitor of GSK-3ß, which may mediate drug resistance, EMT, and damaged DNA and tumor immune response in advanced cancer. In pancreatic cancer models in mice, elraglusib combined with chemotherapy enhanced anti-tumor effects and survival. In a single-arm clinical study, elraglusib/GnP showed antitumor activity and prolonged survival in pts with mPDAC. Methods: Pts with previously untreated mPDAC were randomized 2:1 to GnP plus elraglusib 9.3 mg/kg IV once weekly or GnP in an open-label phase 2 study. The primary endpoint was 1-yr OS in the primary analysis set. Upon study completion, mOS will be the primary endpoint once survival distributions are compared after the 12-month follow-up using log-rank analysis. Secondary endpoints included DCR, ORR, mPFS, and TEAEs/TRAEs. The planned sample size was 207 evaluable pts (130 for elraglusib/GnP and 77 for GnP), assuming 1-yr OS of 55% with elraglusib/GnP and 35% with GnP to achieve 80% power with a chi-square test at a 2-sided 5% α. For OS, nonparametric log-rank test was used with statistical significance at p-value < 0.048. Cytokine/chemokine correlative biomarker assays were performed. The study completed enrollment in February 2024. Results: As of November 15, 2024 (preliminary data cut-off date), the primary analysis set included 155 pts in the elraglusib/GnP arm and 78 pts in the GnP arm, with 52.8% males and 57.5% ECOG PS 1. Median (range) CA 19-9 levels were 1568 U/mL (1 to 381,904 U/mL) in the elraglusib/GnP arm and 1590 U/mL (2 to 501,000 IU/mL) in the GnP arm. The 1-yr OS rate was 43.6% with elraglusib/GnP vs 22.5% with GnP (z-test p = 0.002); the mOS was 9.3 mo with elraglusib/GnP vs 7.2 mo with GnP (HR, 0.63; log rank p = 0.016; see Table). 38.1% of pts on elraglusib/GnP and 19.2% on GnP are censored, with the majority at > 10 months OS. Several biomarkers appear to be predictive for OS including IFNβ and PD-L1. The most common TRAE with elraglusib/GnP was grade 1-2 transient visual impairment in > 60% of patients (vs 9% with GnP). Grade ≥3 TEAEs occurred in 89.7% of pts on elraglusib/GnP and 80.8% on GnP. Most common grade ≥3 TEAEs with elraglusib/GnP (vs GnP) were neutropenia 51.6% (vs 29.5%), anemia 24.5% (vs 29.5%), and fatigue 16.1% (vs 5.1%). Conclusions: The preliminary results showed a statistically significant benefit for 1-yr OS and mOS and favorable trends for ORR and DCR with elraglusib/GnP over GnP, with manageable safety profile. The mOS for GnP is lower relative to MPACT and NAPOLI-3 but comparable to recent real-world meta-analyses, explained by advanced disease burden and higher mortality rate in the first 4 months in our study. Topline analysis (April 2025) and correlative biomarker analysis predictive for OS will be presented. Clinical trial information: NCT03678883 . Preliminary efficacy results. Elraglusib/GnPn=155 GnPn=78 1-year OS, %z-test p=0.002 43.6 22.5 mOS, moHR=0.63; log-rank p=0.016 9.3 7.2 Events, n (%) 96 (61.9) 63 (80.8) mPFS, moHR=0.91; p=NS 5.6 4.9 Events, n (%) 128 (82.6) 70 (89.7) DCR, % 42.6 33.3 ORR, n (%) 43 (27.7) 16 (20.5)
Clinico-radiographic predictors of overall survival in stage II-III pancreatic cancer.
Xu, Qinmei , Toesca, Diego A.S. , Vitzthum, Lucas K. , Jamalian, Arash, Alkım, Emel, Baclay, J.R.M. , Fisher, George A. , Itakura, Haruka , Schueler, Emil , Chang, Daniel T. , Gevaert, Olivier

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2025.43.16_suppl.e16457 Get It

e16457 Background: Patients with inoperable stage II-III pancreatic cancer commonly undergo sequential stereotactic body radiation therapy (SBRT) and chemotherapy. However, there is variability in clinical outcomes, and the predictors of high-risk patients with rapid tumor progression (within 3 months) and poor overall survival (OS) despite treatment are not well characterized. We developed a radiomic (imaging-derived features) signature (RS) that predicts rapid progression. We then investigated clinical characteristics, including pathologic features and treatments received, and RS in a combined analysis to develop and validate the highest-performing model to predict OS from the time of SBRT initiation. We identified the most predictive feature from the combined model that best predicts OS. Methods: In our retrospective study, we examined a cohort of 124 stage II-III pancreatic cancer patients who underwent sequential SBRT and systemic chemotherapy and had pre-treatment pancreatic protocol computed tomography (CT) imaging. We examined 10 clinical features and extracted 900 radiomic features from each segmented tumor per patient using PyRadiomics. Dividing our cohort into training and test sets (60:40), we built a prediction model for rapid tumor progression using radiomic data on the training set (n = 74), applying a LASSO-based algorithm for feature selection and 5-fold cross-validation for parameter optimization. We validated the model performance on the held-out test set (n = 50) and generated the RS for predicting rapid progression. We examined the performance of clinical features and RS in predicting OS in univariate and multivariate Cox regression models. Results: Analysis on our cohort (57 men, 67 women; mean age 67 ± 11 years) generated a 43-feature RS that predicted rapid tumor progression (AUC 0.83, 95% CI: 0.70–0.94) in the test set. High RS was a significant predictor of mortality with hazard ratio (HR) 2.22 (95% CI: 1.32–3.73, p = 0.003) within the first year and 2.85 (95% CI: 1.35–6.03, p = 0.006) thereafter. Non-intensive chemotherapy increased only early mortality risk (HR 1.95, 95% CI: 1.08–3.53, p = 0.03), while older age was significant in later years (HR 1.80, 95% CI: 1.02–3.15, p = 0.04). Conclusions: CT-derived RS accurately predicted rapid tumor progression in stage II-III pancreatic cancer patients undergoing SBRT sequentially with chemotherapy. High RS was the strongest prognostic indicator for increased mortality risk, suggesting its utility for guiding treatment or selection for clinical trials.
National trends in disability-adjusted life years (DALYs) of gastric cancer among elderly (70+ years) from 1990-2021: A global burden of disease study.
Khan, Abdul basit, Kakakhel, Mian Zahid Jan , Ahmad, Husnain , Khawar, Muneeb , Nisar, Muhammad Shahid , Ali, Muhammad Faizan , Jawad, Hamna , Zaied, Mohammad A. , Ikram, Jibran, Ahmed, Faizan , Mannan, Muhammad Shaheer, Ikram, Jibran , Ikram, Jibran , Khan, Abdul basit, Nisar, Mudasar, Ali, Muhammad Faizan , Qadeer, Abdul, Kirchoff, Robert W.

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2025.43.16_suppl.e16456 Get It

e16456 Background: Gastric cancer is one of the significant contributors of mortality and morbidity, especially in older patients. Analyzing national trends in the Disability adjust life years (DALY) helps identify the evolving burden of this disease among patients older than 70 years and highlights the regions requiring particular interventions. Methods: Using Global burden of disease data from 2021, national DALY rates per 100,000 people aged 70 and over with gastric cancer were assessed. The Estimated Annual Percentage Change (EAPCs) with p value taken as a statistical measure of significance, was used to evaluate trends from 1990 to 2021. Results: The analysis displays considerable contrasts in the trends of gastric cancer burden across nations. From 1990 to 2021, a rising trend in DALY EAPC was seen in Egypt (1.01883; 95% CI: -0.1931- 1.958) followed by Honduras (0.3262; 95% CI: 0.0177- 0.7456) and Lesotho (0.2253; 95% CI:-0.1326- 0.6995). Conversely, Austria (-0.7368; 95% CI: -0.7646 to -0.7087), Republic of Korea (-0.7095; 95% CI: -0.7620 to -0.6442) and Singapore (-0.6923; 95% CI: -0.7286 to -0.6553) reported a prominent decline in DALY EAPCs, reflecting significant progress in reducing burden. The DALY rates in 2021 also varied dramatically among nations. Highest DALY rate was observed in Bolivia (4882.7; 95% CI:3782.9- 6349.7) underscoring highest impact on healthcare system. Conversely, Morocco (329.69; 95% CI: 234.64- 410.12) recorded lowest DALY rate indicating comparatively better disease control or lower incidence. Conclusions: While some nations demonstrate remarkable progress in mitigating the burden of gastric cancer, others still face significant challenges. Highest increase in EAPC in Egypt, Honduras and Lesotho whereas significant decline in Austria, Korea, and Singapore indicates areas of target public health efforts. Future research should focus on understanding the causes of these disparities and evaluating the impact of interventions across it. DALY and EPAC. Country 2021 DALY rate EAPC(1990-2021) EAPC, 95% CI Egypt 1272.146 1.018834(highest) -0.193 to 1.959 Honduras 2880.563 0.32617 0.018 to 0.746 Lesotho 1555.79 0.225384 -0.133 to 0.699 Singapore 806.6098 -0.692396 -0.729 to -0.655 Republic of Korea 1961.151 -0.709502 -0.762 to -0.644 Austria 662.5105 -0.736826(lowest) -0.765 to -0.709 Morocco 410.1227(lowest) -0.17817 -0.387 to 0.097 Bolivia 4882.718(highest) -0.32185 -0.473 to -0.103
Gender-specific trends in disability-adjusted life years (DALYs) and mortality rates of pancreatic cancer in adults aged 70 and older: A Global Burden of Disease analysis (1990-2021).
Iqbal, Rabia , Ahmad, Husnain , Kakakhel, Mian Zahid Jan , Ali, Muhammad Faizan , Qadeer, Abdul , Khawar, Muneeb , Zafar, Maha , Kirchoff, Robert W.

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2025.43.16_suppl.e16423 Get It

e16423 Background: Pancreatic cancer (PC) is one of the most aggressive malignancies, disproportionately affecting older adults. Leveraging data from the Global Burden of Disease (GBD), this study investigates gender-specific trends in disability-adjusted life years (DALYs) and mortality rates for PC among adults aged 70 and older from 1990 to 2021. Methods: DALYs and mortality rates associated with PC were extracted for both genders from the GBD-2021 study from 1990 to 2021. The Annual Percentage Change (APC) and the Average Annual Percentage Change (AAPC) were calculated, along with 95% confidence intervals (CI), to assess the statistical significance of the trends using the p-value. Results: In 1990, DALY rates were 837.25 for men and 711.95 for women, increasing to 950.68 and 768.31, respectively, by 2021. Mortality rates followed a similar pattern: men’s rates rose from 52.05 in 1990 to 61.37 in 2021, while women’s increased from 47.31 to 53.40. Men consistently experienced higher burdens than women. The AAPC analysis revealed that men exhibited a steeper rise in both DALYs and mortality rates associated with PC compared to women over the past three decades. Notably, the gender disparity was more evident in DALYs (+0.1929%) than in mortality rates (+0.1358%), with all AAPC values demonstrating statistical significance (p < 0.000001). Following the APC analysis, additional significant trends were identified. Among males, DALY rates demonstrated the most pronounced increase between 1997 and 2021 (APC: 0.5397, 95% CI: 0.5118, 0.5645), whereas in females, the most significant rise occurred from 1990 to 1993 (APC: 0.6593, 95% CI: 0.3608, 1.1016). Conversely, the slowest increase in DALY rates among females was observed between 1993 and 2003 (APC: 0.0925, 95% CI: -0.2053, 0.1641). For mortality rates, the most notable rise in males was observed between 2007 and 2010 (APC: 1.2314, 95% CI: 1.0292, 1.3195), while females experienced their sharpest escalation from 1990 to 1994 (APC: 0.6891, 95% CI: 0.4322, 1.0720). In contrast, the slowest rate of progression in mortality among females occurred between 1993 and 2002 (APC: 0.1736, 95% CI: 0.0180, 0.2368). Conclusions: Over the past three decades, men have experienced a significantly more pronounced rise in DALYs and mortality rates related to PC compared to women.These findings highlight the urgent need for gender-specific interventions to address the growing burden of PC in aging populations. Trends in DALY and mortality rates per 100,000 by gender (1990-2021). Metrics Gender 1990 2021 APC (1990-2021) Daly Rates per 100,000 Male 837.25 950.68 0.4422 Female 711.9 768.31 0.2493 Mortality Rates per 100,000 Male 52.05 61.37 0.5366 Female 47.31 53.40 0.4008
National trends in mortality of pancreatic cancer in adults aged 70 and older across 204 nations: A global burden of disease analysis (1990–2021).
Khan, Abdul basit, Ahmad, Husnain , Kakakhel, Mian Zahid Jan , Ali, Muhammad Faizan , Kamal, Talha, misbah, A.M.EL-mahmoudy Akram Almabrouk, Khawar, Muneeb , Sadiq, Muhammad , Mannan, Muhammad Shaheer, Khan, Abdul basit, Ali, Muhammad Faizan , Kamal, Talha, Ahmed, Faizan , Kirchoff, Robert W.

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2025.43.16_suppl.e16420 Get It

e16420 Background: Pancreatic cancer (PC) typically follows an indolent course and is often diagnosed at an advanced stage, contributing to its high mortality rate, particularly among older adults. Its aggressive nature makes it a significant global health burden, causing substantial mortality across nations. This analysis investigates national mortality trends in adults aged 70 years and older from 1990 to 2021, utilizing data from the Global Burden of Disease (GBD) Study. Methods: We utilized data from the GBD-Study 2021 to report the number of cases and age-standardized rates (per 100,000 population) of PC. To assess mortality trends from 1990 to 2021, we calculated the estimated annual percentage change (EAPC) along with corresponding 95%confidence intervals (CI), providing a robust evaluation of temporal patterns. Results: Over the past three decades, deaths attributable to PC have shown a significant increase globally. In 1990, the United States of America (USA) reported the highest number of PC-related deaths, followed by China and Japan. By 2021, however, China surpassed the USA, becoming the leading contributor to PC mortality, with Japan maintaining its position as the third highest.In 2021, the United Arab Emirates reported the highest mortality rate (148.15), which was more than double its 1990 rate (70.71). The Principality of Monaco (140.87) and Uruguay (129.39) held the second and third highest mortality rates, respectively. The lowest mortality rates were recorded in Mozambique (8.18), Malawi (8.98), and Sao Tome and Principe (9.01).Countries with the largest increases in the EAPC included Turkmenistan (EAPC: 15.16, 95% CI: 10.92, 21.02), Republic of Cabo Verde (EAPC: 13.60, 95% CI: 8.56, 19.48), and Mongolia (EAPC: 4.80, 95% CI: 3.11, 7.26). In contrast, the greatest declines were observed in the Republic of San Marino (EAPC: -0.32, 95% CI: -0.52, -0.07), Guam (EAPC: -0.27, 95% CI: -0.41, -0.13), and Greenland (EAPC: -0.24, 95% CI: -0.44, 0.007). Conclusions: Globally, mortality rates associated with PC among individuals aged 70 and older increased from 1990 to 2021, with particularly notable rises in Turkmenistan, Republic of Cabo Verde, and Mongolia. These findings underscore the critical need for enhanced prevention strategies, improved management, and research to address underlying disparities. Mortality percent change. Metric Region 1990 2021 EAPC with 95% CI (1990-2021) Highest mortality percent change Turkmenistan 1.19 19.34 15.16 (10.92, 21.02) Republic of Cabo Verde 6.47 94.55 13.60 (8.56, 19.48) Mongolia 10.21 59.24 4.80 (3.11, 7.26) Lowest mortality percent change Republic of San Marino 89.48 60.47 -0.32 (-0.52, -0.07) Guam 32.46 23.51 -0.27 (-0.41, -0.13) Greenland 169.52 127.96 -0.24 (-0.44, 0.007)
Regional trends in incidence and prevalence of pancreatic cancer among older adults (70+): A 30-year global burden of disease analysis (1990–2021).
Kakakhel, Mian Zahid Jan , Ahmad, Husnain , Mannan, Muhammad Shaheer, Ali, Muhammad Faizan , Ibrahim, Arwa M, Jawad, Hamna , Idrees, Usama , Khan, Iqra , Qadeer, Abdul , Khawar, Muneeb , Ikram, Jibran, KHAN, A. A. , Rashid, Muhammad, Ibrahim, Arwa M, Ahmed, Faizan , Kirchoff, Robert W.

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2025.43.16_suppl.e16419 Get It

e16419 Background: Pancreatic cancer remains one of the most lethal malignancies worldwide. While high-income regions have long faced higher rates, recent trends show that lower-income regions are also beginning to see an increase. This study explores how pancreatic cancer incidence and prevalence have changed over the past 30 years among adults aged 70 and older assessing regional differences. Methods: We analyzed data from the Global Burden of Disease (GBD) spanning three decades (1990–2021) to assess pancreatic cancer incidence and prevalence rates among adults aged 70+. Data focused on different regions worldwide, grouping them by income levels using the Socio-demographic Index (SDI) and annual changes in incidence and prevalence rates were calculated. Results: In 2021, High-income Asia Pacific had the highest incidence rate at 119.52 per 100,000, whereas Low SDI regions had the lowest at 12.01 per 100,000. High-income regions accounted for the majority of cases, with over 140,000 reported, compared to fewer than 3,000 in the lowest-income areas. Andean Latin America experienced significant APC fluctuations, with a sharp rise from 2015 to 2019 followed by a decline, while High-income North America saw a recent decrease in incidence. Overall, most regions exhibit a steady increase in pancreatic cancer prevalence, with higher AAPCs in Sub-Saharan Africa, North Africa, and parts of Asia, while high-income regions show more moderate increases. Trend analysis reveals significant trends in pancreatic cancer incidence and prevalence among individuals aged 70+. Western Sub-Saharan Africa has the highest Average Annual Percent Change (AAPC) at 2.3248%, indicating the most substantial increase in prevalence from 1990 to 2021, followed by North Africa and the Middle East at 1.9906%. Low-middle SDI regions also show a steady rise with an AAPC of 1.718%, while high-income regions like High-income Asia Pacific report a notable AAPC of 1.595%. Conclusions: Our findings show a concerning rise in pancreatic cancer among older adults, with the most dramatic increases in regions like Western Sub-Saharan Africa and North Africa. To tackle this growing challenge, we need focused efforts on prevention, early detection, and accessible care, especially in lower-resource settings. Incidence percent changes. Metric Region 1990 2021 AAPC (1990-2021) Highest incidence percent change Western Sub-Saharan Africa 7.62 15.38 2.31 North Africa and Middle East 20.97 37.23 1.91 Lowest incidence percent change Caribbean 41.51 41.36 -0.016 Southern Latin America 74.05 73.89 0.006 Highest prevalence percent change Western Sub-Saharan Africa 4.54 9.21 2.32 North Africa and Middle East 12.49 22.77 1.99 Lowest prevalence rate percent change Caribbean 25.02 25.38 0.02 Southern Latin America 44.78 45.45 0.06
National trends in prevalence of pancreatic cancer in adults aged 70 and older: A global burden of disease analysis (1990–2021).
Jajja, Salman Ayub, Mannan, Muhammad Shaheer, Mahmood, Manzoor , Kakakhel, Mian Zahid Jan , Qadeer, Abdul , Khawar, Muneeb , Ahmad, Husnain , Ali, Muhammad Faizan , Ikram, Jibran, Talpur, Abdul Subhan , Mahmood, Muhammad Jasim All, Ali, Muhammad Faizan , Ahmed, Faizan , Kirchoff, Robert W.

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2025.43.16_suppl.e16418 Get It

e16418 Background: Pancreatic cancer remains one of the most fatal malignancies globally, posing a significant burden on older populations. Despite numerous reports on its prevalence, a detailed comparative analysis of national trends among adults aged 70 and older from 1990 to 2021 is scarce. This study seeks to bridge this gap by evaluating prevalence rates using data from the Global Burden of Disease (GBD) study. Methods: Prevalence data for pancreatic cancer in individuals aged 70 years and older were obtained from the GBD-2021 dataset, encompassing 204 countries and territories for the years 1990 and 2021. The Estimated Annual Percent Change (EAPC) and corresponding 95% confidence intervals (CI) were calculated to assess trends over the period from 1990 to 2021. Results: The prevalence of pancreatic cancer has shown a significant increase since 1990, reaching its highest levels in 2021. In 1990, the United States of America (USA) reported the highest prevalence, followed by Japan and China. However, by 2021, Japan ranked first in prevalence, followed by China and the USA. The analysis revealed that in 1990, the highest prevalence rates of pancreatic cancer were observed in Greenland (91.04 per 100,000), followed by Finland (82.57 per 100,000) and Japan (76.30 per 100,000). By 2021, Japan reported the highest prevalence (126.73 per 100,000), followed by Finland (119.20 per 100,000) and Canada (109.22 per 100,000). Despite the observed prevalence rates from 1990 to 2021, Turkmenistan exhibited the most significant increase (EAPC: 15.41, 95% CI: 10.91, 21.41), followed by the Republic of Cabo Verde (EAPC: 13.61, 95% CI: 8.67, 19.59) and Mongolia (EAPC: 4.81, 95% CI: 3.11, 7.20). In contrast, the most significant declines were recorded in the Republic of San Marino (EAPC: -0.308, 95% CI: -0.51, -0.03), followed by Guam (EAPC: -0.24, 95% CI: -0.37, -0.08) and Cuba (EAPC: -0.21, 95% CI: -0.33, -0.09). Conclusions: The prevalence of pancreatic cancer among adults aged 70 and older has increased significantly over the past three decades, with distinct regional patterns. Countries like Japan, China, and the USA continue to report the highest prevalence rates. These findings highlight the urgent need for targeted prevention, screening, and treatment strategies, particularly in high-burden regions, to mitigate the growing impact of pancreatic cancer in aging populations. Prevalence percent changes. Metric Region 1990 2021 EAPC with 95% CI (1990-2021) Highest prevalence percent change Turkmenistan 0.62 10.16 15.41 (10.91, 21.41) Republic of Cabo Verde 3.23 47.18 13.61 (8.67, 19.59) Mongolia 5.25 30.53 4.81 (3.11, 7.20) Lowest prevalence percent change Republic of San Marino 52.61 36.36 -0.308 (-0.51, -0.03) Guam 16.96 12.87 -0.24 (-0.37, -0.08) Cuba 32.65 25.52 -0.21 (-0.33, -0.09)
Evaluating pegylated SN38 (PLX38A) and rucaparib in TP53 wild-type endometrial cancer.
Brennan, Mikayla, Weroha, Saravut J., Hou, Xiaonan , Dowdy, Sean C. , Xu, Conway, Brennan, Mikayla, Kaufmann, Scott H. , Glaser, Gretchen

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: No page available

10.1200/jco.2025.43.16_suppl.e15125 Get It

e15125 Background: Endometrial cancer (EC) is the most common gynecologic malignancy, with endometrioid being the most prevalent histology. Approximately 75% of high-grade endometrioid tumors are TP53 wild-type. During studies testing a novel combination of the PARP inhibitor rucaparib and TOP1 poison SN38 in high-risk primary patient serous and serous-like ECs, a subset of non-serous ECs with normal p53 expression showed unexpected synergy. This suggests broad efficacy in EC, warranting in vivo studies to assess tolerability and efficacy. Given potential overlapping toxicity, a novel formulation, pegylated SN38 (PLX038A), was tested. Methods: Primary patient tumors (n=4) were treated with rucaparib (0µM-25 µM) and SN38 (0µM-0.5 µM) in 3D cell culture experiments. RealTime Glo assessed viability after 3-5 days of drug exposure. Combination indices were determined using the Chou-Talalay method. Tolerability and efficacy were assessed in female SCID-beige mice (n=45) injected with intraperitoneal EC PDX tumors. Mice were randomized to controls, PLX038A (15 mmol/µmol IP, every 14 days), rucaparib (150 mg/kg daily gavage), or combination (same dose and schedule) for 8 weeks. Tolerability was assessed by daily animal weight and total condition score (TCS) from 1 (emaciated, non-ambulatory) to 13 (obese). Weight change more than -20% or TCS < 5 defined moribund criteria. Weekly ultrasound measurements assessed tumor response. Results: All four primary patient tumors exhibited synergy, with a combination index less than 1. Moribund criteria were not met in any mice across all cohorts. The average percent weight change and lowest TCS across cohorts were: rucaparib (-8.51%, min/max -19 to +14%; TCS 6.25, range 5-8, n=8), PLX038A (-3.97%, min/max -19 to +5%; TCS 6.8, range 6-9, n=10), the combination (-5.52%, min/max -15 to +1.8%; TCS 7.18, range 6-8, n=11), and control (+1.61%, range -6 to +8%; TCS 6.5, range 6-7, n=4). Scores were similar between groups, but the slightly lower TCS in the rucaparib cohort was associated with higher tumor burden from ineffective therapy. Tumors in the rucaparib monotherapy group grew similarly to controls. In contrast, the combination therapy cohort exhibited significant regression below baseline during treatment. Conclusions: These findings suggest that the combination of rucaparib and SN38 (PLX038A) is effective in EC primary patient tumor organoids and PDXs with wild-type TP53. No significant negative physiological effects on animal TCS and weight change were observed. No drug-related toxicity was observed in mice receiving combination treatment. Mice receiving combination treatment displayed significant tumor regression below baseline compared to both single agents and control. These data support future exploration of this combination therapy in ECs.
Enhancing educational experiences through standardization of inpatient hematology curriculums.
Lingamaneni, Prasanth , Mina, Syeda A. , Gangat, Naseema , Paludo, Jonas , Godby, Richard

Mayo Clinic

Journal of Clinical Oncology | May 28, 2025 | Volume: 43 | Issue: 16_suppl | Pages: 9024-9024

10.1200/jco.2025.43.16_suppl.9024 Get It

9024 Background: Comprehensive hematology education during fellowship is essential for delivering high-quality healthcare. Variability in individual learning experiences can lead to trainee dissatisfaction and suboptimal clinical acumen. Fellowship programs must strive for a well-rounded and equitable educational experience for all fellows to prepare them for real-world practice in the increasingly dynamic field of hematology. Methods: Hematology fellows (n=30) at Mayo Clinic (Rochester) were invited to complete a survey about the inpatient Fellow Hematology Curriculum (FHC) during 2021-2022. Responses were recorded in a five-point Likert scale and free-text. Using the initial results, we implemented a structured inpatient hematology curriculum starting in 2022 and conducted a post-implementation survey in Spring 2024 to assess its success and sustainability. Results: The initial survey was completed by twenty fellows, with a response rate of 66%. All respondents agreed that the FHC could be improved. Only 45% agreed that structured education is adequately paired with clinical duties. In the open-ended responses, a structured curriculum covering a set list of topics was the most common recommendation given to improve the FHC. This prompted a longitudinal QI initiative to implement standardized rotation-specific lectures created by fellows and distributed to faculty and fellows prior to the associated 4-week rotations. Twelve fellows (40%) completed the post-implementation survey. Summary of key responses are shown in table 1. Although there remained high variability among consultants regarding their engagement in education, significant improvements were noted. Agreement that the curriculum has well-defined objectives for each rotation increased from 25% to 58%. Additionally, 83% of fellows agreed that structured education was effectively paired with clinical duties, up from 45%. Open-ended responses highlighted variability in consultants' utilization of the curriculum but reflected overall satisfaction. Conclusions: The need for a well-structured FHC was identified as a gap in equitable hematology education. This was addressed through a fellow led longitudinal QI project generating easily accessible educational material relevant to weekly themes on inpatient hematology services. The introduction of a structured and clinically relevant curriculum was well-received. Summary of survey responses. Pre-implementation Post-implementation Statement Agreed or strongly agreed (%) Agreed of strongly agreed (%) I know what topics and to what extent I’m expected to learn 25 67 The FHC has well-defined objectives for each rotation 25 55 There is high variability among consultants with engagement in education 95 75 Structured education is paired with clinical duties 45 83 I can easily locate lectures given by hematology consultants 5 42