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1140 citation(s) found for "Núñez, Jorge".

Preclinical feasibility study for transvascular drainage of non-acute subdural hematomas
Liu, Yang , Madhani, Sarosh Irfan , Larco, Jorge Luis Arturo, Shahid, Adnan Hussain , Şenol, Yiğit Can , Lylyk, Pedro , Arturo Larco, Jorge Luis, Lylyk, Pedro N, Savastano, Luis , Liu, Yang , Shahid, Adnan H , Senol, Yigit Can , Larco, Jorge Arturo

Journal of NeuroInterventional Surgery | August 8, 2025 | Volume: 18 | Issue: 5 | Pages: 1355-1363

10.1136/jnis-2025-023794 | PMID 40780814 Get It

Background Non-acute or chronic subdural hematoma (cSDH) is commonly treated with surgical evacuation followed by middle meningeal artery embolization (MMAe). This two step approach increases procedural complexity and redundancy, hospitalization duration, and patient risk. We hypothesized that cSDH could be managed through a single session endovascular procedure and conducted a multimodal preclinical study to evaluate feasibility. Methods We performed three-dimensional heat mapping of hematoma distribution from preoperative CT scans (n=69) and analyzed middle meningeal artery (MMA) and superior sagittal sinus (SSS) anatomy and perforation trajectories using imaging from 107 patients. Rheological properties of 41 SDH samples were assessed using hybrid rheometry and modeled with the Carreau equation. Aspiration feasibility was tested using a 0.027 inch microcatheter (n=16), and dura perforation forces were quantified with a 28 G needle in fresh cadaveric dura (n=10). Results Heat mapping localized cSDH to the parietal convexities (>80% probability) under the branches of the MMA, with limited midline involvement and proximity to the SSS (<10%). The posterior division of the MMA (diameter 1.23±0.23 mm) accommodated a 0.027 inch microcatheter in >90% of cases, with perforation trajectories targeting high probability hematoma zones in 105 of 107 cases. SDH samples exhibited shear thinning viscosity ( η ₀ =172 mPa×s, η ∞ =2.78 mPa×s), with mean aspiration times of 1.21±0.54 min per 10 mL. Perforation forces averaged 0.68±0.24 N in normal and 1.29±0.48 N in calcified dura (P=0.05). Conclusion Anatomical, rheological, and biomechanical data from this study support the feasibility of endovascular drainage of cSDH through the MMA.
Necessary Elements of Intraoperative Cholangiogram: A Call for Synoptic Reporting
Bosley, Maggie E. , Moffett, Jennifer , Porter, Eleah D. , Jorge, Irving , Bloom, Matthew B. , Neff, Lucas P. , Jorge, Irving A

Annals of Surgery Open | July 23, 2025 | Volume: 6 | Issue: 3 | Pages: e599

10.1097/as9.0000000000000599 | PMID 40989875 Get It

Gastro-Entero-Colic Fistula After Successful EUS Guided Gastroenterostomy
Ladd, Antonio Mendoza , Ladna, Michel, Pecha, Luke, Sharzehi, Kaveh , Bhardwaj, Meera., Vargas, Jorge, Gutierrez, Olaya I. Brewer , Schlag, Christoph , Hindryckx, Pieter , Hucl, Tomáš , Sethi, Amrita , Masaryk, Viliam , Khara, Harshit S. , Mendoza Ladd, Antonio , Pérez‐Cuadrado‐Robles, Enrique , Han, Samuel , Vargas, Jorge, Inamdar, Sumant , Pham, Khanh Do-Cong

Journal of Clinical Gastroenterology | July 21, 2025 | Volume: 60 | Issue: 6 | Pages: 543-548

10.1097/mcg.0000000000002178 | PMID 40689823 Get It

Background: EUS-guided gastroenterostomy (EUS-GE) is an effective option for the management of gastric outlet obstruction (GOO). Due to the poor prognosis of patients undergoing it, data on its long-term adverse events (AE) is scarce. Herein, we describe a cohort of patients with gastro-entero-colic fistula (GECF) as a late AE of previously successful EUS-GE. Methods: Patients who developed a GECF after EUS-GE from 10 high-volume centers were analyzed. Information collected included demographic characteristics, indications, clinical and technical success rates, stent type and size, fistula characteristics, management, and outcomes. Results: Sixteen cases were identified. The mean interval from index EUS-GE to the diagnosis of GECF was 4 to 8 weeks. The most common cause of GOO was pancreatic adenocarcinoma (PDAC). The transverse colon was the most common site for the GECF (14 patients). A 20×10 mm lumen apposing metal stent (LAMS) was utilized in 10 patients. Endoscopic management with a variety of modalities was successful in 13 cases. Follow-up interval after endoscopic management of the fistula averaged 2 to 4 weeks. At the time of the manuscript elaboration, 10 patients had died, 5 were alive, and 1 was lost to follow-up. Conclusions: This is the first description of a cohort of patients with GECF after EUS-GE. The exact mechanisms leading to GECF in these cases are unknown. Possible explanations include inadvertent colon puncture during the index procedure and/or entrapment of mesocolon. More data is needed to further characterize this AE.
Nylon Suture Snare for Intraocular Foreign Body Removal: A Case Series
Krivit, Jenna, Romo, Jorge Andrade, Reiter, Gregor S. , Iezzi, Raymond , Giacalone, Joseph C. , Andrade Romo, Jorge, Krivit, Jenna, Ye, Run Zhou

Retina | July 16, 2025 | Volume: 45 | Issue: 12 | Pages: 2424-2428

10.1097/iae.0000000000004608 | PMID 40668961 Get It

Purpose: To describe an improved snare technique for the removal of an intraocular foreign body (IOFB) from the posterior segment. Methods: The snare is fashioned from a 23 or 25-gauge blunt-tipped cannula, a 5-0 or 6-0 nylon suture, and a cotton-tipped applicator. The snare is introduced through a 23 or 25-gauge vitrectomy port and tightened around the IOFB, maintaining a closed system. The IOFB can be extracted from the eye by pulling the cannula and extending the circumferential sclerotomy. Results: Four cases of IOFBs were treated using the improved nylon suture snare technique. Three of the four were traumatic open-globe injuries with retained IOFB, for which the snare technique was suitable for removal of the object. In the fourth case, the snare technique was used to remove a posteriorly dislocated silicone intraocular lens optic. No cases of postoperative retinal detachments or endophthalmitis were observed. Conclusion: This snare is fashioned from readily available, inexpensive materials and provides a safe and reliable method for IOFB removal through the vitrectomy port. By maintaining a closed system during IOFB mobilization and removal, the view through the cornea remains stable and intraocular pressure remains constant. Moreover, the snare can grasp irregularly shaped or large IOFBs.
Molecular Phenogroups in Heart Failure: Large-Scale Proteomics in a Population-Based Cohort
Downie, Carolina G , Shearer, Joseph J. , Kuku, Kayode O. , Kizer, Jorge R. , Psaty, Bruce M. , Joo, Jungnam , Roger, Véronique L. , Bielinski, Suzette , Kizer, Jorge R , Psaty, Bruce M , Joo, Jungnam , Roger, Veronique L , Bielinski, Suzette J.

Circulation: Genomic and Precision Medicine | July 16, 2025 | Volume: 18 | Issue: 4 | Pages: No page available

10.1161/circgen.124.004953 | PMID 40665907 Get It

BACKGROUND: Heart failure (HF) is a heterogeneous syndrome with high mortality. The need for a new taxonomy of HF is recognized; up to now, such phenomapping efforts have primarily used clinical data. Proteomics offers potential for more precise phenotypic identification and mechanistic insights. However, few phenomapping studies have used this approach, and all have focused on targeted cardiovascular proteomics panels and a restricted HF ejection fraction group. METHODS: We measured over 7000 plasma proteins in a population-based cohort of 1351 patients with HF, used k-means clustering to identify distinct phenogroups, and compared their clinical characteristics and all-cause mortality. RESULTS: Three proteomics-defined phenogroups were identified, with substantial differences in survival (phenogroup 1 5-year survival probability, 65% [95% CI, 61%–68%]; phenogroup 2, 45% [40%–51%]; phenogroup 3, 26% [22%–30%]), independent of clinical characteristics. Phenogroups also exhibited differences in several measures suggesting poorer health, including NT-proBNP (N-terminal pro-B-type natriuretic peptide), kidney function, and Meta-Analysis Global Group in Chronic Heart Failure scores, but did not differ by ejection fraction or New York Heart Association class. CONCLUSIONS: Our study demonstrates that molecular phenomapping can stratify patients with HF into distinct subgroups that go beyond predefined clinical classifications.
Multicenter evaluation of blood culture contamination and blood cultures practices in US acute care hospitals: time for standardization
Fabre, Valeria , Hsu, Yea‐Jen , Carroll, Karen C. , Salinas, Alejandra , Abbo, Lilian M. , Bower, Chris , Berry, J. Michael, Degnan, Kathleen, Dhaubhadel, Pragya, Dress, Marci, Feeser, Baevin , Fisher, Mark , Flynn, Cynthia E. , Gettler, Erin , Glasser, Laurel J., Johnson, J. Kristie, Karaba, Sara M. , Kubischta, Alyssa, Landrum, B. Mark, Martinez, Marvin, Mermel, Leonard A. , Pepe, Dana , Qasba, Sonia, Rittmann, Barry , Robinson, Evan D. , Rosa, Rossana , Salinas, Jorge , Shah, Aditya , Schrank, Gregory M. , Spivak, Emily S , Stewart, Kathleen O., Wasylyshyn, Anastasia , Virk, Zunaira, Cosgrove, Sara E. , Abbo, Lilian M , Karaba, Sara M , Fabre, Valeria , Milstone, Aaron M. , Berry, Jennifer, Boyd, Sarah, Diekema, Daniel J. , Ford, Bradley , Glasser, Laurel J., Howard‐Anderson, Jessica , Kim, Justin , Mathers, Amy J. , Moehring, Rebekah W. , O’Horo, John C. , Rodriguez‐Nava, Guillermo , Ryder, Jonathan H. , Shelly, Mark , Talbot, Thomas R. , Schooneveld, Trevor Van , Gadala, Avinash

Journal of Clinical Microbiology | July 11, 2025 | Volume: 63 | Issue: 8 | Pages: No page available

10.1128/jcm.00530-25 | PMID 40643261 Get It

ABSTRACT Clinical and Laboratory Standards Institute (CLSI) recommends a blood culture contamination (BCC) threshold of <3%, with ≤1% considered optimal. However, there is not a standardized definition of BCC, and the effect of multiple definitions on BCC rates or what definitions laboratories use remain unknown. We surveyed 52 hospitals and analyzed 362,078 blood cultures (BCx) collected 1 September 2019 to 31 August 2021 from 62 intensive care units (ICUs) and 231 wards from 48 of these hospitals. We calculated and compared BCC rates using the College of American Pathologists (CAP) or CLSI criteria (both utilize a limited number of skin commensals to define BCC) and the comprehensive National Healthcare Safety Network (NHSN) commensal list. We characterized factors associated with BCC and related outcomes (central-line associated bloodstream infection [CLABSI] and vancomycin use). BCC, BCx positivity, and single BCx rates were monitored by 100%, 39%, and 21% of hospitals, respectively. Hospitals used CAP (65%), CLSI (17%), and NHSN (17%) criteria to define BCC. Mean BCC rate by CAP (CAP-BCC) was 1.38% for ICUs and 0.96% for wards. BCC rates remained similar by CLSI criteria but increased when using NHSN list. Sharing BCC data outside of the laboratory, measuring additional BCx quality indicators, and limiting central catheter-drawn BCx were associated with lower BCC rates. BCC was associated with higher CLABSI rates in ICUs. This study demonstrated variability in laboratory practices and opportunities to optimize BCx stewardship. IMPORTANCE Blood culture contamination (BCC) is associated with patient harm and unnecessary use of healthcare resources. BCC thresholds have been established; however, multiple BCC definitions exist. There is limited data on how BCC rates differ depending on the BCC definition used, what definitions laboratories most commonly use, or their approach to other blood cultures (BCx) quality indicators such as single rates or BCx positivity. A cross-sectional multicenter survey and analysis of BCx data from intensive care unit and wards revealed that most laboratories did not track single BCx or BCx positivity rates and that there was variability in how BCC was defined. Additionally, BCC rates were influenced by the definition used. BCC was associated with increased central-line associated bloodstream infection rates.
Synthetic Patient–Physician Conversations Simulated by Large Language Models: A Multi-Dimensional Evaluation
Haider, Syed Ali , Trabilsy, Maissa , Collaço, Bernardo Gabriele , Wood, Nadia , Tao, Cui , Forte, Antonio J. , Gomez-Cabello, Cesar Abraham, Collaco, Bernardo G , Wood, Nadia , Tao, Cui , Forte, Antonio Jorge , Haider, Syed A , Prabha, Srinivasagam , Gomez-Cabello, Cesar A. , Borna, Sahar , Genovese, Ariana , Bagaria, Sanjay P.

Sensors | July 11, 2025 | Volume: 25 | Issue: 14 | Pages: 4305

10.3390/s25144305 | PMID 40732431 Get It

Background: Data accessibility remains a significant barrier in healthcare AI due to privacy constraints and logistical challenges. Synthetic data, which mimics real patient information while remaining both realistic and non-identifiable, offers a promising solution. Large Language Models (LLMs) create new opportunities to generate high-fidelity clinical conversations between patients and physicians. However, the value of this synthetic data depends on careful evaluation of its realism, accuracy, and practical relevance. Objective: To assess the performance of four leading LLMs: ChatGPT 4.5, ChatGPT 4o, Claude 3.7 Sonnet, and Gemini Pro 2.5 in generating synthetic transcripts of patient–physician interactions in plastic surgery scenarios. Methods: Each model generated transcripts for ten plastic surgery scenarios. Transcripts were independently evaluated by three clinically trained raters using a seven-criterion rubric: Medical Accuracy, Realism, Persona Consistency, Fidelity, Empathy, Relevancy, and Usability. Raters were blinded to the model identity to reduce bias. Each was rated on a 5-point Likert scale, yielding 840 total evaluations. Descriptive statistics were computed, and a two-way repeated measures ANOVA was used to test for differences across models and metrics. In addition, transcripts were analyzed using automated linguistic and content-based metrics. Results: All models achieved strong performance, with mean ratings exceeding 4.5 across all criteria. Gemini 2.5 Pro received mean scores (5.00 ± 0.00) in Medical Accuracy, Realism, Persona Consistency, Relevancy, and Usability. Claude 3.7 Sonnet matched the scores in Persona Consistency and Relevancy and led in Empathy (4.96 ± 0.18). ChatGPT 4.5 also achieved perfect scores in Relevancy, with high scores in Empathy (4.93 ± 0.25) and Usability (4.96 ± 0.18). ChatGPT 4o demonstrated consistently strong but slightly lower performance across most dimensions. ANOVA revealed no statistically significant differences across models (F(3, 6) = 0.85, p = 0.52). Automated analysis showed substantial variation in transcript length, style, and content richness: Gemini 2.5 Pro generated the longest and most emotionally expressive dialogues, while ChatGPT 4o produced the shortest and most concise outputs. Conclusions: Leading LLMs can generate medically accurate, emotionally appropriate synthetic dialogues suitable for educational and research use. Despite high performance, demographic homogeneity in generated patients highlights the need for improved diversity and bias mitigation in model outputs. These findings support the cautious, context-aware integration of LLM-generated dialogues into medical training, simulation, and research.
Negative impact of corticosteroid use on outcome in patients with advanced BTCs treated with cisplatin, gemcitabine, and durvalumab: A large real‐life worldwide population
Prinzi, Federica Lo , Salani, Francesca , Saborowski, Anna , Antonuzzo, Lorenzo , Rossari, Federico , Satake, Tomoyuki, Peeters, Frederik , Pressiani, Tiziana , Kim, Jin Won , Finkelmeier, Fabian , Chiara, Pircher, Chon, Hong Jae , Braconi, Chiara , Qaisar, Aitzaz, Pastorino, Alessandro , Castet, Florian , Parisi, Alessandro , Perkhofer, Lukas , Adeva, Jorge , Spinelli, Gian Paolo , Rodriquenz, Maria Grazia , Leo, Silvana, Alvim, Cecilia Melo, Polito, M.G. , Giacomo, Emanuela Di , Bartalini, L. , Grelli, Giada, Rosa, Antonio De, Lavacchi, Daniele, Ikeda, Masafumi, Dekervel, Jeroen , Balsano, Rita , Tesini, Giulia , Boccaccino, Alessandra , Himmelsbach, Vera, Vogel, Arndt, Rimassa, Lorenza , Casadei‐Gardini, Andrea, Vogel, Arndt , Casadei‐Gardini, Andrea , Rossari, Federico , Prager, Gerald W , Farinea, Giovanni , Niger, Monica , Rimini, Margherita , Antonuzzo, Lorenzo , Lo Prinzi, Federica , Parisi, Alessandro , Casadei-Gardini, Andrea , Finkelmeier, Fabian , Castet, Florian , Adeva, Jorge , Tesini, Giulia , Rimassa, Lorenza , Casadei-Gardini, Andrea , Saborowski, Anna , Pressiani, Tiziana , Jae Chon, Hong , Salani, Francesca , De Rosa, Antonio , Dekervel, Jeroen , Vogel, Arndt , Camera, Silvia , Lucchetti, Jessica , Abidoye, Oluseyi , Rapposelli, Ilario Giovanni , Gallio, Chiara , Tamberi, Stefano , Giordano, Guido , Chiara, Pircher, Tamburini, Emiliano , Yoo, Changhoon , Diana, Anna , Scartozzi, Mario , Prager, Gerald W. , Avallone, Antonio , Schirripa, Marta , Kim, Il Hwan , Oneda, Ester , Verrico, Monica , Couto, Nuno , Chan, Stephen L. , Personeni, Nicola , Garajova, Ingrid , Roque, Ricardo , Ikeda, Masafumi , Niger, Monica , Tonini, Giuseppe , Kang, Minsu , Landriscina, Matteo , Djaballah, Selma Ahcene , Bekaii‐Saab, Tanios , Fornaro, Lorenzo , Masi, Gianluca , Lonardi, Sara , Rimini, Margherita

International Journal of Cancer | July 11, 2025 | Volume: 157 | Issue: 10 | Pages: 2092-2102

10.1002/ijc.70009 | PMID 40641448 Get It

Abstract In recent years, there has been increasing interest in the possible prognostic impact of concomitant medications in patients with cancer treated with immunotherapy combinations. This real‐world analysis aims to evaluate the impact of concomitant medications on survival outcomes in patients with advanced biliary tract cancer (BTCs) treated with cisplatin, gemcitabine and durvalumab (CGD) therapy. The study cohort included patients with a diagnosis of advanced BTCs who were taking concomitant medications for their comorbidities before the start of CGD. The primary objectives were overall survival (OS) and progression‐free survival (PFS). The initial population consisted of 666 patients, who were retrospectively collected from 41 sites in 12 countries. Data on concomitant medications were available for 493 patients. After a median follow‐up of 8.8 months (95% CI: 7.8–9.8), patients who did not take steroids (prednisone >10 mg/day or equivalent) or nonsteroidal anti‐inflammatory drugs (NSAIDs) and opioids, before the start of CGD, had longer OS and PFS in univariate analysis. The multivariate analysis confirmed longer OS for patients who did not take steroids. Patients who did not take steroids had an OS of 14.8 months (95% CI: 13.1–29.1) versus 5.0 months (95% CI: 2.14–11.32) of patients who took prednisone >10 mg/day or equivalent. No differences were reported in terms of overall response rate (ORR), disease control rate (DCR) ( p = 1.0 and p = .16, respectively), and safety profile between the two groups. Our analysis suggests that patients who did not receive steroids before the start of GCD had longer survival and highlighted the relevance of balancing concomitant medications and chemoimmunotherapy.
Assessment of a Deep Learning Model Trained on Permanent Pathology for the Classification of Squamous Cell Carcinoma in Mohs Frozen Sections: Lessons Learned
Choudhary, Anirudh , Nassir, Shams , Yousif, Miranda , Hughes, Alysia , Kechter, Jacob , Leibovit-Reiben, Zachary , Stockard, Alyssa , Vidal, Nahid Y. , Rios-Duarte, Jorge A, Kechter, Jacob A, Rios‐Duarte, Jorge A. , Iyer, Ravishankar K. , Leibovit‐Reiben, Zachary , Mangold, Aaron R.

Dermatologic Surgery | July 9, 2025 | Volume: 52 | Issue: 1 | Pages: 31-35

10.1097/dss.0000000000004758 | PMID 40631753 Get It

BACKGROUND There is a scarcity of artificial intelligence models trained on frozen pathology. One way to expand the clinical utility of models trained on permanent pathology is by applying them to frozen sections and fine-tune based on weaknesses. OBJECTIVE To qualitatively evaluate a deep learning model trained on permanent pathology to classify squamous cell carcinoma on Mohs surgery frozen sections to learn model shortcomings and inform retraining and fine-tuning. MATERIALS AND METHODS The authors trained a model for classification of tumor on 746 skin biopsy slides and tested it on 15 Mohs surgery frozen sections. The authors estimated performance metrics and compared the regions of interest generated by the model with the original H&E slides. RESULTS The model achieved an AUC-ROC of 0.985 and 0.796 for tumor classification in permanent pathology and in frozen sections, respectively. Regions of interest for frozen sections with scarce tumor areas were inaccurate, focusing on normal tissue for slides classified as false negative, or highlighting structures different from tumor (e.g., inflammation, muscle, and nerves) for slides classified as true positive. CONCLUSION Deep anatomical structures more commonly present in Mohs frozen pathology might represent data out-of-distribution for models trained on permanent pathology, potentially leading to inadequate model outputs.
The impact of molecular alterations in patients with advanced biliary tract cancer receiving cisplatin, gemcitabine, and durvalumab: a large, real-life, worldwide population
Prinzi, Federica Lo , Rizzato, Mario Domenico , Saborowski, Anna , Antonuzzo, Lorenzo , Rossari, Federico , Satake, Tomoyuki, Peeters, Frederik , Pressiani, Tiziana , Finkelmeier, Fabian , Braconi, Chiara , Qaisar, Aitzaz, Pirrone, Chiara, Castet, Florian , Parisi, Alessandro , Scartozzi, Mario, Corallo, Salvatore , Perkhofer, Lukas , Adeva, Jorge , Spinelli, Gian Paolo , Rodriquenz, Maria Grazia , Leo, Silvana, Alvim, Cecilia Melo, Roque, Ricardo , Salani, Francesca , Rosa, Antonio De, Lavacchi, Daniele, Dekervel, Jeroen , Niger, Monica, Balsano, Rita , Esposito, Luca, Boccaccino, Alessandra , Himmelsbach, Vera, Zanuso, Valentina , Vogel, Arndt, Rimassa, Lorenza , Casadei‐Gardini, Andrea , Vogel, Arndt , Lo Prinzi, Federica , Rizzato, Mario Domenico , Saborowski, Anna , Antonuzzo, Lorenzo , Rossari, Federico , Peeters, Frederik , Pressiani, Tiziana , Lucchetti, Jessica , Kim, Jin Won , Abidoye, Oluseyi , Rapposelli, Ilario Giovanni , Finkelmeier, Fabian , Giordano, Guido , Nichetti, Federico , Jae Chon, Hong , Qaisar, Aitzaz , Pirrone, Chiara , Castet, Florian , Tamburini, Emiliano , Parisi, Alessandro , Scartozzi, Mario , Avallone, Antonio , Corallo, Salvatore , Schirripa, Marta , Oneda, Ester , Verrico, Monica , Adeva, Jorge , Chan, Stephen L , Spinelli, Gian Paolo , Personeni, Nicola , Garajova, Ingrid , Rodriquenz, Maria Grazia , Roque, Ricardo , Farinea, Giovanni , Salani, Francesca , De Rosa, Antonio , Camera, Silvia , Ikeda, Masafumi , Dekervel, Jeroen , Niger, Monica , Kang, Minsu , Bekaii-Saab, Tanios S , Esposito, Luca , Boccaccino, Alessandra , Djaballah, Selma Ahcene , Zanuso, Valentina , Masi, Gianluca , Vogel, Arndt , Lonardi, Sara , Rimassa, Lorenza , Casadei-Gardini, Andrea , Casadei-Gardini, Andrea , Rimini, Margherita , Fornaro, Lorenzo , Vivaldi, Caterina , Kim, Jin Won , Abidoye, Oluseyi , Tamberi, Stefano , Nichetti, Federico , Chon, Hong Jae , Yoo, Changhoon , Diana, Anna , Prager, Gerald W. , Kim, Il Hwan , Chan, Stephen L. , Ikeda, Masafumi , Niger, Monica , Tonini, Giuseppe , Bekaii‐Saab, Tanios , Landriscina, Matteo , Malapelle, Umberto , Pepe, Francesco , Lonardi, Sara

JNCI: Journal of the National Cancer Institute | July 3, 2025 | Volume: 117 | Issue: 10 | Pages: 2029-2043

10.1093/jnci/djaf155 | PMID 40608977 Get It

Abstract Background Cisplatin, gemcitabine, and durvalumab combination is a standard first-line treatment for advanced biliary tract cancer. This study aimed to assess the impact of genetic alterations on outcomes in patients with advanced biliary tract cancer treated with cisplatin, gemcitabine, and durvalumab in real-world clinical practice. Methods Patients with unresectable, locally advanced, or metastatic biliary tract cancer treated with cisplatin and gemcitabine plus durvalumab across 39 centers in 11 countries in Europe, the United States, and Asia were included in this analysis. Results The cohort included 513 patients with advanced biliary tract cancer. The 5 most frequently altered genes were TP53 (22.1%), KRAS (13.7%), CDKN2A/B (13.6%), ARID1A (12.2%), and IDH1 (9.2%). In multivariate analysis, SMAD4 mutations were associated with improved progression-free survival (PFS) (hazard ratio [HR] = 0.49, P = .018) and overall survival (HR = 0.11, P = .023), while TP53 mutations were linked to worse PFS (HR = 1.62, P = .0047) and TERT mutations to worse overall survival (HR = 8.92, P = .0012). No other genomic alterations were statistically associated with outcomes. Subgroup analysis showed that TP53 mutations negatively affected PFS and overall survival in intrahepatic cholangiocarcinoma, while KRAS mutations were associated with poorer PFS in extrahepatic cholangiocarcinoma. No gene alterations were linked to outcomes in gallbladder cancer. Conclusions This large-scale analysis, with comprehensive molecular profiling, supports the positive prognostic impact of SMAD4 mutations for PFS and overall survival and highlights the negative prognostic roles of TP53 (PFS) and TERT (overall survival) mutations, providing valuable insights for personalized treatment strategies in biliary tract cancer.