{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T17:05:54Z","timestamp":1773335154285,"version":"3.50.1"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T00:00:00Z","timestamp":1773273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>The objective of this study was to investigate the feasibility of administering neoadjuvant stereotactic ablative body radiotherapy (SABR) for the purpose of increasing pancreatic tumor perfusion, hence potentially improving systemic drug delivery in patients with resectable (RPC) or borderline-resectable pancreatic cancer (BRPC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Neoadjuvant SABR was administered to RPC (n=1) and BRPC (n=5) patients with a dose prescription of 27\u201330 Gy in 3 fractions and a dose boost up to 45 Gy to the metabolically active areas of the tumor. Computed tomography perfusion (CTP) studies were acquired at baseline, 6 hours after delivering the first SABR fraction (post-1\n                      <jats:sup>st<\/jats:sup>\n                      -fx), and 3\u20134 weeks after completing SABR (post-RT). For BRPC patients, studies were also acquired after neoadjuvant chemotherapy (post-cx), which preceded SABR. Using a deconvolution-based CTP software, the tumor blood flow (BF), blood volume (BV), permeability-surface area product (PS), and extravascular extracellular volume (V\n                      <jats:sub>e<\/jats:sub>\n                      ) were calculated at each study instance. Additionally, a surrogate measure of the tumor cell density (CD) was derived from V\n                      <jats:sub>e<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The post-1\n                      <jats:sup>st<\/jats:sup>\n                      -fx tumor BF was significantly higher than baseline (p=0.010) for the RPC patient and 2 other BRPC patients who had acquired a pre-treatment baseline scan. The post-RT BF, PS, V\n                      <jats:sub>e<\/jats:sub>\n                      were also significantly higher than baseline (p&amp;lt;0.05), and a decrease in CD could be observed after the initial treatment (% decrease relative to baseline: post-cx for BRPC = 23%; post-RT for RPC = 14%). The BRPC patients showed a subsequent decrease in CD at post-RT relative to post-cx (&amp;lt;5%). For all BRPC patients, the post-1\n                      <jats:sup>st<\/jats:sup>\n                      -fx BF was significantly higher relative to post-cx (p=0.033), followed by a non-significant decline at post-RT. Conversely, the PS showed a significant decrease at post-1\n                      <jats:sup>st<\/jats:sup>\n                      -fx relative to post-cx (p&amp;lt;0.001), although the post-RT changes showed no consistent trend. The V\n                      <jats:sub>e<\/jats:sub>\n                      was still significantly higher at post-RT relative to post-cx (p=0.015).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study provides preliminary evidence that delivering SABR in the neoadjuvant setting for RPC and BRPC patients can induce acute and sustained increases in pancreatic tumor perfusion. Additionally, this study shows that tumor CD may have adequate sensitivity as a biomarker for monitoring patient response to standard-of-care therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1677923","type":"journal-article","created":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T05:27:58Z","timestamp":1773293278000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Analyzing the effect of neoadjuvant stereotactic ablative body radiotherapy on pancreatic tumor perfusion using computed tomography perfusion"],"prefix":"10.3389","volume":"16","author":[{"given":"Jin-Young","family":"Bang","sequence":"first","affiliation":[{"name":"Department of Medical Biophysics, Western University","place":["London, ON, Canada"]},{"name":"London Health Sciences Centre","place":["London, ON, Canada"]},{"name":"Robarts Research Institute","place":["London, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Breadner","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre","place":["London, ON, Canada"]},{"name":"Department of Oncology, Western University","place":["London, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Nguyen","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre","place":["London, ON, Canada"]},{"name":"Department of Oncology, Western University","place":["London, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton","family":"Skaro","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre","place":["London, ON, Canada"]},{"name":"Department of Surgery, Western University","place":["London, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Goodman","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre","place":["London, ON, Canada"]},{"name":"Department of Oncology, Western University","place":["London, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Welch","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre","place":["London, ON, Canada"]},{"name":"Department of Oncology, Western University","place":["London, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Tsvetkova","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre","place":["London, ON, Canada"]},{"name":"Department of Oncology, Western University","place":["London, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Lenehan","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre","place":["London, ON, Canada"]},{"name":"Department of Oncology, Western University","place":["London, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Leslie","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre","place":["London, ON, Canada"]},{"name":"Department of Surgery, Western University","place":["London, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ephraim","family":"Tang","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre","place":["London, ON, Canada"]},{"name":"Department of Surgery, Western University","place":["London, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas","family":"Quan","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre","place":["London, ON, Canada"]},{"name":"Department of Surgery, Western University","place":["London, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Sey","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre","place":["London, ON, Canada"]},{"name":"Department of Medicine, Western University","place":["London, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Yan","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre","place":["London, ON, Canada"]},{"name":"Department of Medicine, Western University","place":["London, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danielle","family":"Porplycia","sequence":"additional","affiliation":[{"name":"Department of Oncology, London Health Sciences Centre","place":["London, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Sinfield","sequence":"additional","affiliation":[{"name":"Department of Oncology, London Health Sciences Centre","place":["London, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stewart","family":"Gaede","sequence":"additional","affiliation":[{"name":"London Health Sciences Centre","place":["London, ON, Canada"]},{"name":"Department of Oncology, Western University","place":["London, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting-Yim","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Western University","place":["London, ON, Canada"]},{"name":"Department of Oncology, Western University","place":["London, ON, Canada"]},{"name":"Lawson Research Institute","place":["London, ON, Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21820","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.02.012","article-title":"Pancreatic cancer: changing epidemiology and new approaches to risk assessment, early detection, and prevention","volume":"164","author":"Stoffel","year":"2023","journal-title":"Gastroenterology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djaa004","article-title":"Recent trends in the incidence and survival of stage 1A pancreatic cancer: A surveillance, epidemiology, and end results analysis","volume":"112","author":"Blackford","year":"2020","journal-title":"J Natl Cancer Inst"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1245\/ASO.2006.08.011","article-title":"Borderline resectable pancreatic cancer: Definitions, management, and role of preoperative therapy","volume":"13","author":"Varadhachary","year":"2006","journal-title":"Ann Surg Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-009-0408-6","article-title":"Pretreatment assessment of resectable and borderline resectable pancreatic cancer: Expert consensus statement","volume":"16","author":"Callery","year":"2009","journal-title":"Ann Surg Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2017.0131","article-title":"Pancreatic adenocarcinoma, version 2.2017: Clinical practice guidelines in Oncology","volume":"15","author":"Tempero","year":"2017","journal-title":"JNCCN J Natl Compr Cancer Network"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-73525-y","article-title":"The actual 5-year survivors of pancreatic ductal adenocarcinoma based on real-world data","volume":"10","author":"Bengtsson","year":"2020","journal-title":"Sci Rep"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/SLA.0000000000004147","article-title":"Actual five-year survival after upfront resection for pancreatic ductal adenocarcinoma: who beats the odds","volume":"275","author":"Strobel","year":"2022","journal-title":"Ann Surg"},{"key":"B9","doi-asserted-by":"publisher","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":"B10","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12113677","article-title":"Neoadjuvant treatments for pancreatic ductal adenocarcinoma: where we are and where we are going","volume":"12","author":"Coppola","year":"2023","journal-title":"J Clin Med"},{"key":"B11","volume-title":"Pancreatic cancer: pathogenesis, prevention and treatment","author":"Sarkar","year":"2007"},{"key":"B12","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3390\/genes11010006","article-title":"Metastasis in pancreatic ductal adenocarcinoma: Current standing and methodologies","volume":"11","author":"Pereira","year":"2020","journal-title":"Genes (Basel)"},{"key":"B13","volume-title":"Pancreatic cancer and tumor microenvironment","author":"Grippo","year":"2012"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/cancers6042137","article-title":"Desmoplasia and chemoresistance in pancreatic cancer","volume":"6","author":"Schober","year":"2014","journal-title":"Cancers (Basel)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0b013e3181dbf647","article-title":"alpha-smooth muscle actin expressing stroma promotes an aggressive tumor biology in pancreatic ductal adenocarcinoma","volume":"39","author":"Fujita","year":"2010","journal-title":"Pancreas"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1186\/s12876-015-0340-0","article-title":"Fibroblast activation protein-\u03b1-expressing fibroblasts promote the progression of pancreatic ductal adenocarcinoma","volume":"15","author":"Kawase","year":"2015","journal-title":"BMC Gastroenterol"},{"key":"B17","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/s00535-008-2249-7","article-title":"Mechanisms of pancreatic fibrosis and applications to the treatment of chronic pancreatitis","volume":"43","author":"Shimizu","year":"2008","journal-title":"J Gastroenterol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0000000000000196","article-title":"Pancreatic stellate cell: Physiologic role, role in fibrosis and cancer","volume":"31","author":"Apte","year":"2015","journal-title":"Curr Opin Gastroenterol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-10671-w","article-title":"Collagen complexity spatially defines microregions of total tissue pressure in pancreatic cancer","volume":"7","author":"Nieskoski","year":"2017","journal-title":"Sci Rep"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/s00261-021-03190-w","article-title":"Quantitative CT perfusion imaging in patients with pancreatic cancer: a systematic review","volume":"47","author":"Perik","year":"2022","journal-title":"Abdominal Radiology"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-09-0414","article-title":"Decreased blood flow with increased metabolic activity: A novel sign of pancreatic tumor aggressiveness","volume":"15","author":"Komar","year":"2009","journal-title":"Clin Cancer Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1126\/science.1171362","article-title":"Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer","volume":"324","author":"Olive","year":"2009","journal-title":"Science"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1456","article-title":"High interstitial fluid pressure - An obstacle in cancer therapy","volume":"4","author":"Heldin","year":"2004","journal-title":"Nat Rev Cancer"},{"key":"B24","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1038\/s41575-020-0300-1","article-title":"Pancreatic cancer stroma: an update on therapeutic targeting strategies","volume":"17","author":"Hosein","year":"2020","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2010.226092","article-title":"Stromal biology and therapy in pancreatic cancer","volume":"60","author":"Neesse","year":"2011","journal-title":"Gut"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2009.12.013","article-title":"Tumor perfusion increases during hypofractionated short-course radiotherapy in rectal cancer: Sequential perfusion-CT findings","volume":"94","author":"Janssen","year":"2010","journal-title":"Radiotherapy Oncol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2006.10.005","article-title":"Acute tumor vascular effects following fractionated radiotherapy in human lung cancer: In vivo whole tumor assessment using volumetric perfusion computed tomography","volume":"67","author":"Ng","year":"2007","journal-title":"Int J Radiat Oncol Biol Phys"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1080\/13651820500468034","article-title":"Neoadjuvant chemoradiation in patients with pancreatic adenocarcinoma","volume":"8","author":"Krempien","year":"2006","journal-title":"HPB"},{"key":"B29","unstructured":"Effect of radiation on interstitial fluid pressure and oxygenation in a human tumor xenograft\n          \n          \n            \n              Znati\n              CA\n            \n            \n              Rosenstein\n              M\n            \n            \n              Boucher\n              Y\n            \n            \n              Epperly\n              MW\n            \n            \n              Bloomer\n              WD\n            \n          \n          \n          1996"},{"key":"B30","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3978\/j.issn.2305-5839.2014.11.17","article-title":"Stereotactic ablative radiotherapy: Aim for a cure of cancer","volume":"3","author":"Chang","year":"2015","journal-title":"Ann Transl Med"},{"key":"B31","article-title":"CT perfusion techniques and applications in stroke and cancer","volume-title":"Computed tomography: approaches, applications, and operations","author":"Lee","year":"2019"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-08-0715","article-title":"Combination of antiangiogenesis with chemotherapy for more effective cancer treatment","volume":"7","author":"Ma","year":"2008","journal-title":"Mol Cancer Ther"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.46.3653","article-title":"Normalizing tumor microenvironment to treat cancer: Bench to bedside to biomarkers","volume":"31","author":"Jain","year":"2013","journal-title":"J Clin Oncol"},{"key":"B34","unstructured":"Anti-angiogenic immunotherapy\n          \n          \n            \n              Schoenfeld\n              JD\n            \n            \n              Dranoff\n              G\n            \n          \n          \n          2011"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-1871","article-title":"Impact of stromal sensitivity on radiation response of tumors implanted in SCID hosts revisited","volume":"70","author":"Garc\u00eda-Barros","year":"2010","journal-title":"Cancer Res"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1126\/science.1082504","article-title":"Tumor response to radiotherapy regulated by endothelial cell apoptosis","volume":"300","author":"Garcia-Barros","year":"2003","journal-title":"Science"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1011252","article-title":"Enhanced perfusion following exposure to radiotherapy: A theoretical investigation","volume":"20","author":"K\u00f6ry","year":"2024","journal-title":"PLoS Comput Biol"},{"key":"B38","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/B978-0-12-818561-2.00007-2","article-title":"Effects of radiation on endothelial barrier and vascular integrity","volume-title":"Tissue barriers in disease, injury and regeneration","author":"Bouten","year":"2021"},{"key":"B39","doi-asserted-by":"publisher","first-page":"6043","DOI":"10.1038\/s41598-019-42519-w","article-title":"Intra- and interobserver reproducibility of pancreatic perfusion by computed tomography","volume":"9","author":"Garcia","year":"2019","journal-title":"Sci Rep"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2021.0017","article-title":"Pancreatic adenocarcinoma, version 2.2025, NCCN clinical practice guidelines in oncology","volume":"8","author":"Tempero","year":"2010","journal-title":"J Natl Compr Cancer Network"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2020.101073","article-title":"Blood flow contributions to cancer metastasis","volume":"23","author":"Font-Clos","year":"2020","journal-title":"iScience"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/cas.12477","article-title":"Prevention of cancer recurrence in tumor margins by stopping microcirculation in the tumor and tumor-host interface","volume":"105","author":"Hori","year":"2014","journal-title":"Cancer Sci"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1677923\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T05:28:06Z","timestamp":1773293286000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1677923\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,12]]},"references-count":42,"alternative-id":["10.3389\/fonc.2026.1677923"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1677923","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,12]]},"article-number":"1677923"}}