{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T13:55:58Z","timestamp":1787061358653,"version":"build-2736575974"},"reference-count":36,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ohio State University College"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Neoadjuvant therapy (NT) is increasingly utilized for patients with localized pancreatic ductal adenocarcinoma (PDAC). Toxicities during NT are common, often leading to the inability to undergo surgical resection, yet risk factors for attrition are poorly understood. Therefore, we sought to evaluate the impact of baseline frailty on outcomes of patients with PDAC undergoing NT. Methods: All patients with potentially resectable (PR) or borderline resectable (BR) PDAC who initiated neoadjuvant chemotherapy and\/or chemoradiation between 2019 and 2025 at a single institution were assessed retrospectively in an intention-to-treat fashion. The association between frailty as defined by the modified 11-item frailty index (mFI-11) and receipt of surgical resection as well as other secondary endpoints was assessed. Comprehensive functional frailty assessments were prospectively obtained in a subset of patients. Results: Among 252 eligible patients, the median age was 67 years, 56.7% were male, 90.9% were White, 49.6% had PR disease, and 5.2% were frail according to mFI-11. After a median 3.6 months of NT, 62.7% underwent surgical resection. Frail individuals had worse performance status and increased comorbidities compared with non-frail patients. On multivariable analysis, male sex, BR anatomic staging, initial use of Gemcitabine + nab-paclitaxel, and frailty (OR 0.09; 95%CI 0.02\u20130.44) were associated with reduced odds of undergoing resection. Along with increased baseline CA 19-9 levels, frailty was independently associated with worse overall survival (HR 3.00; 95%CI 1.46\u20136.20). Among 39 patients who underwent formal functional frailty assessment, only abnormal posture was associated with lower odds of surgical resection following NT (OR, 0.22; 95% CI, 0.05\u20130.92), and no aspects of functional frailty were associated with overall survival. Conclusions: Among patients with localized PDAC initiating NT, frailty as assessed by mFI-11 was associated with reduced odds of undergoing surgical resection and worse overall survival. Future research should focus on efforts to improve functional status during NT.<\/jats:p>","DOI":"10.3390\/cancers17244030","type":"journal-article","created":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:15:21Z","timestamp":1766049321000},"page":"4030","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Impact of Frailty on the Outcomes of Patients with Pancreatic Cancer Undergoing Neoadjuvant Therapy"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1186-8744","authenticated-orcid":false,"given":"Nicholas R.","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Leuschner","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9743-4293","authenticated-orcid":false,"given":"Amanda K.","family":"Walsh","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla","family":"Gault","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber","family":"Ingram","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex B.","family":"Blair","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7994-9870","authenticated-orcid":false,"given":"Timothy M.","family":"Pawlik","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Dillhoff","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2373-8433","authenticated-orcid":false,"given":"Jordan M.","family":"Cloyd","sequence":"additional","affiliation":[{"name":"Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,18]]},"reference":[{"key":"ref_1","first-page":"10","article-title":"Cancer Statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e211031","DOI":"10.1001\/jamanetworkopen.2021.1031","article-title":"National Trends in the Use of Neoadjuvant Therapy Before Cancer Surgery in the US from 2004 to 2016","volume":"4","author":"Aquina","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/s41571-023-00746-1","article-title":"Neoadjuvant Therapy for Pancreatic Cancer","volume":"20","author":"Springfeld","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41575-023-00856-2","article-title":"Preoperative Chemotherapy, Radiotherapy and Surgical Decision-Making in Patients with Borderline Resectable and Locally Advanced Pancreatic Cancer","volume":"21","author":"Stoop","year":"2024","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Orlandi, E., Vecchia, S., Anselmi, E., Toscani, I., Guasconi, M., Perrone, G., Citterio, C., Banchini, F., and Giuffrida, M. (2025). Neoadjuvant Treatment in Localized Pancreatic Cancer of the Elderly: A Systematic Review of the Current Literature. Cancers, 17.","DOI":"10.3390\/cancers17050747"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ejca.2021.10.023","article-title":"Neoadjuvant Therapy or Upfront Surgery for Resectable and Borderline Resectable Pancreatic Cancer: A Meta-Analysis of Randomised Controlled Trials","volume":"160","author":"Janssen","year":"2022","journal-title":"Eur. J. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.hpb.2021.10.010","article-title":"Multi-Specialty Physician Perspectives on Barriers and Facilitators to the Use of Neoadjuvant Therapy for Pancreatic Ductal Adenocarcinoma","volume":"24","author":"Schreiber","year":"2022","journal-title":"HPB"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1001\/jamasurg.2024.5191","article-title":"Best Practices for Delivering Neoadjuvant Therapy in Pancreatic Ductal Adenocarcinoma","volume":"160","author":"Cloyd","year":"2025","journal-title":"JAMA Surg."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Jain, A.J., Maxwell, J.E., Katz, M.H.G., and Snyder, R.A. (2023). Surgical Considerations for Neoadjuvant Therapy for Pancreatic Adenocarcinoma. Cancers, 15.","DOI":"10.3390\/cancers15164174"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e237099","DOI":"10.6004\/jnccn.2023.7099","article-title":"Failure to Undergo Resection Following Neoadjuvant Therapy for Resectable Pancreatic Cancer: A Secondary Analysis of SWOG S1505","volume":"22","author":"Cloyd","year":"2024","journal-title":"J. Natl. Compr. Canc. Netw."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.cger.2010.08.008","article-title":"Frailty Defined by Deficit Accumulation and Geriatric Medicine Defined by Frailty","volume":"27","author":"Rockwood","year":"2011","journal-title":"Clin. Geriatr. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.1002\/cam4.2157","article-title":"Association between Frailty Syndrome and Survival in Patients with Pancreatic Adenocarcinoma","volume":"8","author":"Holmes","year":"2019","journal-title":"Cancer Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/jgs.18054","article-title":"Patient-Reported Geriatric Assessment-Based Frailty Index among Older Adults with Gastrointestinal Malignancies","volume":"71","author":"Giri","year":"2023","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/annonc\/mdu540","article-title":"The Prevalence and Outcomes of Frailty in Older Cancer Patients: A Systematic Review","volume":"26","author":"Handforth","year":"2015","journal-title":"Ann. Oncol."},{"key":"ref_15","first-page":"362","article-title":"Frailty and Cancer: Implications for Oncology Surgery, Medical Oncology, and Radiation Oncology","volume":"67","author":"Ethun","year":"2017","journal-title":"CA Cancer J. Clin."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.jss.2013.01.021","article-title":"Accumulating Deficits Model of Frailty and Postoperative Mortality and Morbidity: Its Application to a National Database","volume":"183","author":"Velanovich","year":"2013","journal-title":"J. Surg. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.avsg.2022.04.007","article-title":"Increased Frailty Associated with Higher Long-Term Mortality after Major Lower Extremity Amputation","volume":"86","author":"Cotton","year":"2022","journal-title":"Ann. Vasc. Surg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"M146","DOI":"10.1093\/gerona\/56.3.M146","article-title":"Frailty in Older Adults: Evidence for a Phenotype","volume":"56","author":"Fried","year":"2001","journal-title":"J. Gerontol. A. Biol. Sci. Med. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/1047-2797(91)90005-W","article-title":"The Cardiovascular Health Study: Design and Rationale","volume":"1","author":"Fried","year":"1991","journal-title":"Ann. Epidemiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1016\/S0140-6736(25)00261-2","article-title":"Pancreatic Cancer","volume":"405","author":"Stoop","year":"2025","journal-title":"Lancet"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1097\/XCS.0000000000000971","article-title":"Impact of Neoadjuvant Therapy for Pancreatic Cancer: Transatlantic Trend and Postoperative Outcomes Analysis","volume":"238","author":"Davis","year":"2024","journal-title":"J. Am. Coll. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Reni, M., Macchini, M., Orsi, G., Procaccio, L., Malleo, G., Carconi, C., Rapposelli, I.G., Bencardino, K., Scartozzi, M., and Balzano, G. (2025). Preoperative mFOLFIRINOX versus PAXG for Stage I\u2013III Resectable and Borderline Resectable Pancreatic Ductal Adenocarcinoma (PACT-21 CASSANDRA): Results of the First Randomisation Analysis of a Randomised, Open-Label, 2 \u00d7 2 Factorial Phase 3 Trial. Lancet, Epub ahead of printing.","DOI":"10.1016\/S0140-6736(25)01685-X"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1200\/JCO.19.02274","article-title":"Preoperative Chemoradiotherapy Versus Immediate Surgery for Resectable and Borderline Resectable Pancreatic Cancer: Results of the Dutch Randomized Phase III PREOPANC Trial","volume":"38","author":"Versteijne","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1097\/SLA.0000000000004155","article-title":"Surgical Outcome Results From SWOG S1505: A Randomized Clinical Trial of mFOLFIRINOX Versus Gemcitabine\/Nab-Paclitaxel for Perioperative Treatment of Resectable Pancreatic Ductal Adenocarcinoma","volume":"272","author":"Ahmad","year":"2020","journal-title":"Ann. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1097\/XCS.0000000000000499","article-title":"Tolerability, Attrition Rates, and Survival Outcomes of Neoadjuvant FOLFIRINOX for Nonmetastatic Pancreatic Adenocarcinoma: Intent-to-Treat Analysis","volume":"236","author":"Fong","year":"2023","journal-title":"J. Am. Coll. Surg."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Dickey, E.M., Min, L., Dhawan, A., Martos, M., Franceschi, D., Livingstone, A.S., Hosein, P., Terrero, G., Datta, J., and Merchant, N. (2025). Factors Driving Attrition from Neoadjuvant Therapy to Pancreatectomy in Localized Pancreatic Cancer. Ann. Surg. Oncol., Epub ahead of printing.","DOI":"10.1245\/s10434-025-18664-0"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"17000","DOI":"10.1038\/s41598-025-02365-5","article-title":"Novel Modified Frailty Index Predicts Completion of Adjuvant Chemotherapy in Resectable Pancreatic Cancer in a Dual Center Study","volume":"15","author":"Funamizu","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_28","first-page":"695.e11","article-title":"Impact of the Preoperative Modified 5-Item Frailty Index on the Efficacy of Neoadjuvant Chemotherapy in Patients with Muscle Invasive Bladder Cancer","volume":"43","author":"Goto","year":"2025","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"106206","DOI":"10.1016\/j.ijsu.2021.106206","article-title":"Skeletal Muscle Wasting during Neoadjuvant Therapy as a Prognosticator in Patients with Esophageal and Esophagogastric Junction Cancer: A Systematic Review and Meta-Analysis","volume":"97","author":"Wang","year":"2022","journal-title":"Int. J. Surg."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.ygyno.2025.08.020","article-title":"Real-World Outcomes of Neoadjuvant Chemotherapy for Advanced Ovarian Cancer: What Happens to Patients Who Never Undergo Surgery?","volume":"201","author":"Bruce","year":"2025","journal-title":"Gynecol. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1097\/SLA.0000000000005878","article-title":"Effects of a Pragmatic Home-Based Exercise Program Concurrent with Neoadjuvant Therapy on Physical Function of Patients with Pancreatic Cancer: The PancFit Randomized Clinical Trial","volume":"278","author":"Parker","year":"2023","journal-title":"Ann. Surg."},{"key":"ref_32","first-page":"2275","article-title":"Physical Activity and Exercise during Preoperative Pancreatic Cancer Treatment","volume":"27","author":"Parker","year":"2019","journal-title":"Support. Care Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"166","DOI":"10.3390\/pathophysiology31010013","article-title":"A Multiomics Assessment of Preoperative Exercise in Pancreatic Cancer Survivors Receiving Neoadjuvant Therapy: A Case Series","volume":"31","author":"Nemkov","year":"2024","journal-title":"Pathophysiology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1016\/j.surg.2023.12.022","article-title":"Minimally Invasive Pancreaticoduodenectomy: A Favorable Approach for Frail Patients with Pancreatic Cancer","volume":"175","author":"Farah","year":"2024","journal-title":"Surgery"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1007\/s00423-024-03483-w","article-title":"Modified 5-Item Frailty Index (mFI-5) May Predict Postoperative Outcomes after Pancreatoduodenectomy for Pancreatic Cancer","volume":"409","author":"Khalid","year":"2024","journal-title":"Langenbecks Arch. Surg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.surg.2014.12.006","article-title":"The Charlson Age Comorbidity Index Predicts Early Mortality after Surgery for Pancreatic Cancer","volume":"157","author":"Ferrone","year":"2015","journal-title":"Surgery"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/24\/4030\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T09:30:45Z","timestamp":1766050245000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/17\/24\/4030"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,18]]},"references-count":36,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["cancers17244030"],"URL":"https:\/\/doi.org\/10.3390\/cancers17244030","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,18]]}}}