{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T10:24:10Z","timestamp":1776248650820,"version":"3.50.1"},"reference-count":29,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:00:00Z","timestamp":1776211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy. Next-generation sequencing (NGS) enables molecular characterization and may identify clinically actionable alterations; however, real-world multicenter data linking genomic subgroups to survival outcomes remain limited. We aimed to characterize the molecular landscape of NGS-tested PDAC in a Turkish multicenter cohort and evaluate the association of key molecular alterations, including KRAS status and KRAS variant subgroups, with survival outcomes. Methods: We conducted a multicenter retrospective cohort study including patients with pathologically diagnosed PDAC between 2017 and 2025 who underwent tumor-based NGS in routine clinical practice. Overall survival (OS) was calculated from the date of metastasis, defined as the date of diagnosis for de novo metastatic disease and the date of first documented distant recurrence for recurrent cases. Progression-free survival (PFS) was calculated from the initiation of first-line systemic therapy for metastatic disease to progression or death. Survival was estimated using the Kaplan\u2013Meier method and compared using the log-rank test. Multivariable Cox proportional hazards models were constructed for OS and PFS using clinically relevant covariates selected a priori. Results: A total of 98 patients underwent molecular profiling, and survival analyses were performed in 92 patients with available OS\/PFS data. KRAS mutations were detected in 83.7% (82\/98) of patients, with predominant variants G12D (47.6%), G12V (30.5%), and G12R (12.2%). TP53 mutations were present in 59.2% (58\/98) of tumors, and all tumors were microsatellite stable. Tumor mutational burden data were available for 72 patients; the median TMB was 3.83 mutations\/Mb, and 15.3% of evaluable tumors had a TMB \u2265 10 mutations\/Mb. Excluding KRAS, clinically actionable alterations were identified in 4.1% of patients, whereas an additional 32.7% harbored potentially actionable or investigational alterations. Median OS was 14.0 months (95% CI, 11.7\u201316.3), and median PFS was 6.0 months (95% CI, 4.3\u20137.7). In unadjusted analyses, OS and PFS did not differ significantly according to KRAS mutation status (OS, p = 0.967; PFS, p = 0.652), TP53 mutation status (OS, p = 0.404; PFS, p = 0.510), or KRAS variant subgroup (OS, p = 0.332; PFS, p = 0.194). In multivariable Cox analyses, KRAS mutation status was not independently associated with OS (aHR 1.13, 95% CI 0.56\u20132.28; p = 0.727) or PFS (aHR 1.09, 95% CI 0.59\u20132.01; p = 0.780), whereas ECOG performance status remained the strongest adverse clinical factor. Conclusions: In this multicenter real-world PDAC cohort, the molecular landscape was dominated by KRAS and TP53 alterations, whereas clinically actionable non-KRAS alterations were identified in only a minority of patients. After adjustment for major clinical covariates, KRAS mutation status was not independently associated with OS or PFS. Molecular profiling may still be useful for identifying uncommon potentially targetable alterations; however, larger clinically annotated multicenter studies are needed to better define its prognostic and treatment-directing value in routine practice.<\/jats:p>","DOI":"10.3390\/curroncol33040216","type":"journal-article","created":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T09:15:59Z","timestamp":1776244559000},"page":"216","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Profiling and Survival Outcomes in Pancreatic Ductal Adenocarcinoma: A Multicenter Real-World Study from Turkey"],"prefix":"10.3390","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0930-5025","authenticated-orcid":false,"given":"Selami","family":"Bayram","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, Memorial Antalya Hospital, 07025 Antalya, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4462-6393","authenticated-orcid":false,"given":"Bahad\u0131r","family":"K\u00f6yl\u00fc","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Medical Oncology, School of Medicine, Ko\u00e7 University, 34450 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4587-0726","authenticated-orcid":false,"given":"Maral Martin","family":"M\u0131ldano\u011flu","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Istanbul Medipol University, 34810 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7663-6182","authenticated-orcid":false,"given":"Mustafa Serkan","family":"Alemdar","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Medikal Park Antalya Hospital, 07160 Antalya, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2212-1412","authenticated-orcid":false,"given":"Tahir","family":"Yerlikaya","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Antalya State Hospital, 07070 Antalya, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fatih","family":"Sel\u00e7ukbiricik","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Medical Oncology, School of Medicine, Ko\u00e7 University, 34450 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmet","family":"Bilici","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Istanbul Medipol University, 34810 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali Murat","family":"Tatli","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Faculty of Medicine, Istanbul Medipol University, 34810 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mustafa","family":"Ozdogan","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Memorial G\u00f6ztepe Hospital, 34634 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,15]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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