JNCI Cancer Spectrum最新文献

{"title":"Alcohol consumption, polygenic risk score, and the risk of colorectal neoplasia.","authors":"Ruojin Fu, Xuechen Chen, Teresa Seum, Michael Hoffmeister, Hermann Brenner","doi":"10.1093/jncics/pkaf017","DOIUrl":"10.1093/jncics/pkaf017","url":null,"abstract":"<p><strong>Background: </strong>Excess alcohol consumption is associated with increased risk of colorectal cancer, but the evidence on the individual and joint effects of alcohol consumption and genetic risk on the occurrence of various stages of colorectal carcinogenesis is limited.</p><p><strong>Methods: </strong>We evaluated the associations of alcohol consumption and a polygenic risk score based on 140 colorectal cancer related loci with findings of colorectal neoplasia among 4662 participants in the German screening colonoscopy program. Analyses were conducted by multiple logistic regression. We determined genetic risk equivalents to quantify the effect of alcohol consumption in terms of the difference in polygenic risk score conveying equivalent risk.</p><p><strong>Results: </strong>Moderate and high (12 to <25 g/d and ≥25 g/d) alcohol consumption was associated with increased risk of advanced colorectal neoplasia (adjusted odds ratio = 1.28, 95% CI = 1.03 to 1.58, and adjusted odds ratio = 1.44, 95% CI = 1.14 to 1.81, respectively), while associations with any colorectal neoplasia were weaker. No significant interactions between alcohol consumption and polygenic risk score were observed. Participants with high alcohol consumption in the highest polygenic risk score tertile had a 3.4-fold increased risk of advanced neoplasia compared with individuals with low or no alcohol consumption in the lowest polygenic risk score tertile. The estimated impact of high alcohol consumption on the risk of advanced neoplasia was equivalent to the risk increase by a 26-percentile-higher polygenic risk score (genetic risk equivalent = 26, 95% CI = 9 to 44).</p><p><strong>Conclusion: </strong>High alcohol consumption and polygenic risk score have a major impact on the risk of advanced colorectal neoplasia. The estimated preventive impact of avoiding high alcohol consumption is as strong as the impact of having a substantially lower polygenic risk.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibiotic treatment and survival in patients with resected, early-stage pancreatic ductal adenocarcinoma receiving chemotherapy.","authors":"Emma Gong, Daniel J Fulop, Joyce Serebrenik, Arielle J Labiner, Deirdre J Cohen, Keith M Sigel, Aimee L Lucas","doi":"10.1093/jncics/pkaf024","DOIUrl":"10.1093/jncics/pkaf024","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic ductal adenocarcinoma is a clinically challenging malignancy largely because of its chemoresistance. Bacteria within the pancreatic ductal adenocarcinoma microbiome may mediate chemoresistance, suggesting that alteration of the microbiome with antibiotics could improve chemotherapy response.</p><p><strong>Methods: </strong>We utilized the Surveillance, Epidemiology, and End Results Program-Medicare database to select patients with resected, early-stage pancreatic ductal adenocarcinoma diagnosed between 2007 and 2017. The primary outcome of this study was overall survival. Receipt of antibiotic treatment within 1 month after adjuvant chemotherapy initiation was determined from Medicare claims data. Propensity scores were used to match patients who received antibiotics with patients who did not receive antibiotics. The Kaplan-Meier method was used to calculate 5-year overall survival rates, and Cox regression analysis was used to assess the association between receiving antibiotics and overall survival. All hypotheses were 2 sided.</p><p><strong>Results: </strong>Of the 712 patients with resected, early-stage pancreatic ductal adenocarcinoma, 629 (88.3%) were treated with adjuvant gemcitabine and 177 (24.9%) received antibiotics in the 1 month following chemotherapy initiation. The mean (SD) age at diagnosis was 73.7 (5.1) years, and patients were mostly women, White, and from metropolitan areas in the northeastern or western United States. A total of 143 propensity score-matched pairs were evaluated. Among patients treated with gemcitabine, antibiotic treatment was associated with a 37% improvement in overall survival and a 30% improvement in cancer-specific survival.</p><p><strong>Conclusions: </strong>Antibiotic treatment in the 1 month following adjuvant gemcitabine initiation was associated with improved survival. These findings provide additional support for the hypothesis that antibiotic treatment may alter the pancreatic microbiome in a manner that reduces chemoresistance, potentially improving pancreatic ductal adenocarcinoma outcomes.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11917212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional outcomes after primary vs delayed robot-assisted radical prostatectomy following active surveillance.","authors":"Christian Corsini, Pietro Scilipoti, Andri Wilberg Orrason, Rolf Gedeborg, Marcus Westerberg, Pär Stattin","doi":"10.1093/jncics/pkaf020","DOIUrl":"10.1093/jncics/pkaf020","url":null,"abstract":"<p><strong>Background: </strong>It is unknown if a period of active surveillance before prostatectomy for prostate cancer (PCa) worsens functional outcomes. The aim of this study was to compare functional outcomes after primary vs delayed robot-assisted radical prostatectomy.</p><p><strong>Methods: </strong>We included men registered in the National Prostate Cancer Register of Sweden with low and favorable intermediate-risk PCa who underwent robot-assisted prostatectomy in 2018-2020 and had filled a questionnaire on patient-reported outcome measures. Multivariable logistic regression analysis was used to compare the functional outcomes of primary and delayed prostatectomy.</p><p><strong>Results: </strong>2571 men underwent primary, and 921 men underwent delayed prostatectomy. Delayed prostatectomy was not associated with reduced overall quality of life (adjusted Odds Ratio [OR] 1.04; 95% confidence interval [CI] 0.71-1.55) or erectile dysfunction (adjusted OR 0.90, 95% CI 0.69-1.22). Urinary incontinence was slightly more common after delayed prostatectomy (15% vs 11%; adjusted OR 1.38, 95% CI 0.91-2.01). There were weak associations between time to prostatectomy and urinary symptoms and bother, with a 3% annual increase in the risk for urinary incontinence (adjusted OR 1.03; 95% CI 0.94-1.13).</p><p><strong>Conclusion: </strong>These results suggest that a period on active surveillance before robot-assisted radical prostatectomy has little detrimental effect on functional outcomes. Since only around half of men on active surveillance will transit to prostatectomy, these outcomes represent a worst-case scenario for men who start active surveillance. These results support the use of active surveillance for men with low-risk and favorable intermediate-risk PCa.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilizing proton therapy to reduce health-care disparities among patients with breast cancers.","authors":"Kristin Hsieh, Jehee Isabelle Choi, Anthony Nehlsen, Jana Fox, Richard Bakst, Julie Bloom, Irini Yacoub, Arpit M Chhabra, Audrey Saitta, Manjeet Chadha, Sheryl Green, Deborah Marshall, Charles B Simone","doi":"10.1093/jncics/pkaf003","DOIUrl":"10.1093/jncics/pkaf003","url":null,"abstract":"","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":"9 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143491894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking the rise of early-onset gastrointestinal cancers: a call to action.","authors":"Benjamin A Weinberg, Caitlin C Murphy, David R Freyer, K Leigh Greathouse, Jan K Blancato, Elena M Stoffel, Julia L Drewes, Anne Blaes, John M Salsman, Y Nancy You, Hannah Arem, Reetu Mukherji, Priyanka Kanth, Xin Hu, Anne Fabrizio, Marion L Hartley, Marios Giannakis, John L Marshall","doi":"10.1093/jncics/pkaf002","DOIUrl":"10.1093/jncics/pkaf002","url":null,"abstract":"<p><p>Since the early 1990s, there has been a dramatic rise in gastrointestinal cancers diagnosed in patients under age 50 for reasons that remain poorly understood. The most significant change has been the increase in incidence rates of early-onset colorectal cancer, especially rates of left-sided colon and rectal cancers. Increases in gastric, pancreatic, and other gastrointestinal cancer diagnoses have further contributed to this trend. We formed a multidisciplinary Think Tank to develop a strategic, coordinated approach to studying early-onset gastrointestinal cancers. This area of research is challenging given multifactorial etiologies. We focused on epidemiology and the environment, the microbiome, and survivorship as key pillars to structure a research framework. We advocate a comprehensive strategy to (1) use existing biospecimens, especially those collected longitudinally, with correlation to exposures (the exposome); (2) standardize microbiome specimen collection and analyses of blood, tissue, and stool specimens to minimize contamination and biases; (3) prioritize mechanistic studies to evaluate findings from biomarker studies; and (4) explore the unique survivorship needs of this young population. These recommendations build upon prior efforts with the goal of streamlining research into this important field of study while minimizing redundant efforts. We hope that our findings serve as a clarion call to motivate others to discover why young individuals are being diagnosed with gastrointestinal cancers at such an alarming rate and how to best support those who have been diagnosed.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11804804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outpatient palliative care and end-of-life care intensity: linking Massachusetts Cancer Registry with All-Payer Claims Database.","authors":"Nancy L Keating, Joel S Weissman, Alexi A Wright, Robert Wolf, Susan Gershman, Richard Knowlton, John Z Ayanian","doi":"10.1093/jncics/pkaf010","DOIUrl":"10.1093/jncics/pkaf010","url":null,"abstract":"<p><strong>Background: </strong>Early palliative care is associated with better outcomes for patients with advanced-stage cancers. Using a novel data linkage, we assessed outpatient palliative care use before death and its association with end-of-life care intensity and variation across 8 provider networks in Massachusetts.</p><p><strong>Methods: </strong>We linked Massachusetts Cancer Registry and the All-Payer Claims Database for individuals with commercial insurance, Medicaid, or Medicare Advantage diagnosed with colorectal, lung, prostate, and breast cancers from 2010 to 2013 who died by December 31, 2014. We characterized outpatient palliative care visits in the 6 months before death and identified end-of-life hospitalizations, emergency department visits, intensive care unit admissions, chemotherapy, no/late hospice enrollment, and in-hospital deaths. We used logistic regression to assess factors associated with outpatient palliative care and ordinal logistic regression with provider network fixed effects to assess the association of palliative care with a composite measure summing individual end-of-life intensity measures.</p><p><strong>Results: </strong>Among 6279 decedents, 11.3% had at least 1 outpatient palliative care visit. Palliative care use varied across provider networks from 6.0% to 19.3%. In adjusted analyses, younger age, longer duration from diagnosis to death, death in 2012-2014 vs 2010, and provider network were associated with palliative care visits (all P values less than .05). End-of-life care intensity varied across provider networks. Patients with palliative care visits had lower adjusted odds of receiving intensive end-of-life care (adjusted odds ratio = 0.62 per additional measure of end-of-life intensity, 95% CI = 0.53 to 0.72).</p><p><strong>Conclusions: </strong>Outpatient palliative care use varied substantially among regional provider networks and was associated with less intensive end-of-life care.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028926","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in melanoma survival-a GEM study.","authors":"Tharani Murali, Matthew Schwartz, Adam Z Reynolds, Li Luo, Grace Ridgeway, Klaus J Busam, Anne E Cust, Hoda Anton-Culver, Richard P Gallagher, Roberto Zanetti, Stefano Rosso, Lidia Sacchetto, Colin B Begg, Irene Orlow, Nancy E Thomas, Marianne Berwick","doi":"10.1093/jncics/pkaf005","DOIUrl":"10.1093/jncics/pkaf005","url":null,"abstract":"<p><p>Sex differences in melanoma are prominent, with female having a significant survival advantage. However, it is unclear why we see this survival advantage. Here, we investigate the relationship between sex, clinicopathologic variables, and melanoma specific survival in 1753 single primary melanomas from patients in the GEM (Genes, Environment, and Melanoma) study. Using Cox proportional hazard models and formal mediation analysis, the effect of sex on survival is explained largely by differences in the clinicopathologic features of tumors at diagnosis. Specifically, we find evidence that 86.5% of the effect of sex on melanoma survival is mediated by differences in age at diagnosis, Breslow thickness, ulceration, mitoses, and site (hazard ratio [HR] = 1.85, P < .001). This analysis indicates that the female survival advantage in melanoma is not primarily due to a direct effect of sex (HR = 1.19, P = .42) but is largely a result of an indirect effect of sex mediated by clinicopathologic features.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11812020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142970890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abdominal visceral and subcutaneous adipose tissue associations with postmenopausal breast cancer incidence.","authors":"Jennifer W Bea, Heather M Ochs-Balcom, Celina I Valencia, Zhao Chen, Robert M Blew, Kimberly E Lind, Bette J Caan, Denise J Roe, Thomas E Rohan, Katherine W Reeves, JoAnn E Manson, Tarah Ballinger, Kerryn W Reding, Shawna Follis, Shelby G Ziller, Andrew O Odegaard","doi":"10.1093/jncics/pkaf007","DOIUrl":"10.1093/jncics/pkaf007","url":null,"abstract":"<p><strong>Background: </strong>Obesity, classified by body mass index (BMI), is associated with higher postmenopausal breast cancer (BCa) risk. Yet, the associations between abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) with BCa are unclear.</p><p><strong>Methods: </strong>We assessed BCa associations with abdominal VAT and SAT in a prospective cohort of postmenopausal women without a history of cancer and with 27 years follow-up (N = 9950), during which all new cancers were adjudicated. Dual-energy x-ray absorptiometry scans assessed adiposity at baseline, year 3, and year 6. Competing-risks multivariable sub-hazard ratios (SHR), with adjustments for sociodemographic, behavioral, reproductive, and anthropometric characteristics, were estimated for baseline and time-dependent associations between VAT, SAT, and incident BCa.</p><p><strong>Results: </strong>Participants averaged 63.3 ± 7.4 years of age and a BMI of 28.20 ± 5.72 kg/m2 at baseline. The models included 738 incident BCa case patients (N = 593 invasive; N = 145 in situ). Baseline VAT and SAT area were associated with statistically significantly increased BCa risk, by 36% and 19%, respectively. Increasing VAT/SAT ratio was associated with an 8% increase in incident BCa. Time-dependent models produced similar results. VAT and VAT/SAT associated BCa risk was highest for African American/Black women, although not statistically significantly different from other groups. Quartiles (Q) of VAT/SAT were also explored; the SHR for Q4 compared with Q1 was 1.49 (95% CI = 1.18 to 1.87).</p><p><strong>Conclusion: </strong>Higher abdominal VAT and SAT are associated with an increased risk of postmenopausal BCa, and VAT/SAT may provide a distinctive risk estimate. Potential racial and ethnic differences require replication in a larger sample (Women's Health Initiative; NCT00000611; https://clinicaltrials.gov/study/NCT00000611).</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11879126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cancer outcomes and cardiopulmonary toxicities for Black patients with breast cancer treated with proton therapy.","authors":"Gurbani Singh, Sravya Koduri, Manaahil Rao, Meira Kidorf, Sarah Ruff, Akshar Patel, Søren M Bentzen, Elizabeth Nichols, Sarah McAvoy, Melissa A L Vyfhuis","doi":"10.1093/jncics/pkae129","DOIUrl":"10.1093/jncics/pkae129","url":null,"abstract":"<p><strong>Background: </strong>Black women have a 40% higher breast cancer mortality rate than White women and are at a higher risk of acquiring cardiovascular disease. Proton therapy can be used to mitigate cardiac radiation exposure; however, proton therapy remains a scarce resource in the United States. We report on the cardiovascular profiles of patients undergoing proton therapy to determine the potential benefit of the therapy for Black women compared with patients of other races.</p><p><strong>Methods: </strong>We retrospectively analyzed 599 patients with breast cancer who received proton therapy from June 2016 to December 2021 at the Maryland Proton Treatment Center. A variety of sociodemographic, disease, and treatment variables were analyzed using descriptive statistics.</p><p><strong>Results: </strong>With a median follow-up of 26 months (range = 0.47-90 months), Black patients made up 31.6% of the population and presented with higher rates of hypertension (P < .001), cardiopulmonary conditions (P < .001), and a higher median body mass index (P = .015) compared with the other cohort, a trend that persisted at the time of post-proton therapy follow-up. Black women had higher rates of triple-negative disease (P < .001), with subsequent greater receipt of neoadjuvant chemotherapy (P = .039). Pulmonary events were 2.6 times more likely to occur in Black patients than in the non-Black cohort after proton therapy (odds ratio = 2.60, 95% CI = 1.39 to 4.88; P = .003).</p><p><strong>Conclusions: </strong>Black women presenting for proton therapy had higher baseline risks of cardiovascular co-morbidities combined with more aggressive breast cancer biology and a subsequent 2.6-fold increased risk of pulmonary events after proton therapy. Our findings support the use of advanced radiation techniques as a means of sparing important organs at risk, especially in historically marginalized populations.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12257934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of undifferentiated carcinomas of the pancreas with and without osteoclast-like giant cells.","authors":"Jamie N Mills, Valerie Gunchick, Jake McGue, Zhaoping Qin, Chandan Kumar-Sinha, Filip Bednar, Noah Brown, Jiaqi Shi, Aaron M Udager, Timothy Frankel, Mark M Zalupski, Vaibhav Sahai","doi":"10.1093/jncics/pkae097","DOIUrl":"10.1093/jncics/pkae097","url":null,"abstract":"<p><strong>Background: </strong>Undifferentiated carcinoma (UC) is a rare subtype of pancreatic cancer distinguished from UC with osteoclast-like giant cells (UC-OGC) in 2019, affecting interpretation of literature that does not distinguish these subtypes. We sought to identify translationally relevant differences between these 2 variants and compared with pancreatic ductal adenocarcinoma.</p><p><strong>Methods: </strong>We characterized clinical and multiomic differences between UC (n = 32) and UC-OGC (n = 15) using DNA sequencing, RNA sequencing, and multiplex immunofluorescence and compared these findings with pancreatic ductal adenocarcinoma.</p><p><strong>Results: </strong>Characteristics at diagnosis were similar between UC and UC-OGC, though the latter was more resectable (P = .009). Across all stages, median overall survival was shorter for UC than for UC-OGC (0.4 years vs 10.8 years, respectively; P = .003). This shorter survival was retained after stratification by resection, albeit without statistical significance (1.8 years vs 11.9 years, respectively; P = .08). In a subset of patients with available tissue, the genomic landscape was similar among UC (n = 9), UC-OGC (n = 5), and pancreatic ductal adenocarcinoma (n = 159). Bulk RNA sequencing was deconvoluted and, along with multiplex immunofluorescence in UC (n = 13), UC-OGC (n = 5), and pancreatic ductal adenocarcinoma (n = 16), demonstrated statistically significantly increased antigen-presenting cells, including M2 macrophages and natural killer cells, and decreased cytotoxic and regulatory T cells in UC and UC-OGC vs pancreatic ductal adenocarcinoma. Findings were similar between UC and UC-OGC , except for decreased regulatory T cells in UC-OGC (P = .04).</p><p><strong>Conclusions: </strong>In this series, UC was more aggressive than UC-OGC, with these variants having more antigen-presenting cells and fewer regulatory T cells than pancreatic ductal adenocarcinoma, suggesting potential for immune-modulating therapies in the treatment of these pancreatic cancer subtypes.</p>","PeriodicalId":14681,"journal":{"name":"JNCI Cancer Spectrum","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700618/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}