{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:10:37Z","timestamp":1788844237969,"version":"build-2803163510"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"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>Background<\/jats:title>\n                    <jats:p>Patients with glioblastoma frequently present contrast-enhancing lesions at radiotherapy completion; however, their clinical significance and optimal management remain unclear. This study evaluated the clinical outcomes of early salvage surgery performed immediately after radiotherapy completion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective single-center study included adult patients with supratentorial glioblastoma receiving standard chemoradiotherapy. The initial extent of resection was classified using postoperative magnetic resonance imaging according to the RANO\n                      <jats:italic>resect<\/jats:italic>\n                      framework. Early salvage surgery was defined as repeat craniotomy for safely resectable post-radiotherapy contrast-enhancing lesions before maintenance chemotherapy initiation. The Kaplan\u2013Meier method and Cox proportional hazards models were used to analyze overall survival (OS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Post-radiotherapy contrast-enhancing lesions were identified in 118 of 174 eligible patients (67.8%). Patients with lower initial RANO\n                      <jats:italic>resect<\/jats:italic>\n                      classes more frequently demonstrated enlarging contrast-enhancing lesions at radiotherapy completion. Early salvage surgery was performed in 17 patients (14.4%). Gross total resection (0 cm\n                      <jats:sup>3<\/jats:sup>\n                      residual) and near-total resection (&amp;lt;1 cm\n                      <jats:sup>3<\/jats:sup>\n                      residual) were achieved in 5 and 4 patients, respectively. Histopathological examination revealed viable tumor components with treatment-related changes in all resected specimens. Multivariate analysis of patients with post-radiotherapy contrast-enhancing lesions identified an independent association between early salvage surgery and longer OS (hazard ratio = 0.440,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.021). Surgical morbidity included postoperative decline in Karnofsky Performance Status in two patients and wound-related complications in two patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Early salvage surgery for post-radiotherapy contrast-enhancing lesions was independently associated with longer OS and may represent a feasible treatment option in carefully selected patients within multidisciplinary glioblastoma management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1872660","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:26:44Z","timestamp":1788841604000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical outcomes of early salvage surgery for residual or enlarging contrast-enhancing lesions after radiotherapy in patients with glioblastoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Shigeru","family":"Yamaguchi","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Faculty of Medicine, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukitomo","family":"Ishi","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Faculty of Medicine, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Nishioka","sequence":"additional","affiliation":[{"name":"Department of Radiation-Oncology, Faculty of Medicine, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michinari","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Faculty of Medicine, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Sawaya","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Faculty of Medicine, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sogo","family":"Oki","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Faculty of Medicine, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiji","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Faculty of Medicine, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zenichi","family":"Tanei","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology, Hokkaido University Hospital","place":["Sapporo, Japan"]},{"name":"Department of Cancer Pathology, Faculty of Medicine, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Surgical Pathology, Hokkaido University Hospital","place":["Sapporo, Japan"]},{"name":"Department of Cancer Pathology, Faculty of Medicine, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidefumi","family":"Aoyama","sequence":"additional","affiliation":[{"name":"Department of Radiation-Oncology, Faculty of Medicine, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miki","family":"Fujimura","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Faculty of Medicine, Hokkaido University","place":["Sapporo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3171\/2011.2.jns10998","article-title":"An extent of resection threshold for newly diagnosed glioblastomas","volume":"115","author":"Sanai","year":"2011","journal-title":"J Neurosurg"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3171\/2015.5.JNS142087","article-title":"The influence of maximum safe resection of glioblastoma on survival in 1229 patients: Can we do better than gross-total resection","volume":"124","author":"Li","year":"2016","journal-title":"J Neurosurg"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noac193","article-title":"Prognostic validation of a new classification system for extent of resection in glioblastoma: A report of the Rano Resect Group","volume":"25","author":"Karschnia","year":"2023","journal-title":"Neuro Oncol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.1373","article-title":"Association of the extent of resection with survival in glioblastoma: A systematic review and meta-analysis","volume":"2","author":"Brown","year":"2016","journal-title":"JAMA Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3171\/2014.7.JNS132449","article-title":"Residual tumor volume versus extent of resection: Predictors of survival after surgery for glioblastoma","volume":"121","author":"Grabowski","year":"2014","journal-title":"J Neurosurg"},{"key":"B6","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1001\/jamaoncol.2019.6143","article-title":"Association of maximal extent of resection of contrast-enhanced and non-contrast-enhanced tumor with survival within molecular subgroups of patients with newly diagnosed glioblastoma","volume":"6","author":"Molinaro","year":"2020","journal-title":"JAMA Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noac255","article-title":"Impact of maximal extent of resection on postoperative deficits, patient functioning, and survival within clinically important glioblastoma subgroups","volume":"25","author":"Gerritsen","year":"2023","journal-title":"Neuro Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3171\/2016.7.JNS16396","article-title":"The effects of new or worsened postoperative neurological deficits on survival of patients with glioblastoma","volume":"127","author":"Rahman","year":"2017","journal-title":"J Neurosurg"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.18718","article-title":"Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: A randomized clinical trial","volume":"318","author":"Stupp","year":"2017","journal-title":"JAMA"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1093\/noajnl\/vdae176","article-title":"Impact of tumor-treating fields on the survival of Japanese patients with newly diagnosed glioblastoma: A multicenter, retrospective cohort study","volume":"6","author":"Kanamori","year":"2024","journal-title":"Neuro Oncol Adv"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-025-05268-7","article-title":"Rapid early progression of glioblastoma: Evaluation of a novel prognostic radiologic biomarker","volume":"176","author":"Guzzino","year":"2025","journal-title":"J Neuro Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.23736\/S0390-5616.18.04463-6","article-title":"The prognostic improvement of add-on bevacizumab for progressive disease during concomitant temozolomide and radiation therapy in patients with glioblastoma and anaplastic astrocytoma","volume":"64","author":"Yamaguchi","year":"2020","journal-title":"J Neurosurg Sci"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000133398.11870.9a","article-title":"Immediate post-radiotherapy changes in Malignant glioma can mimic tumor progression","volume":"63","author":"de Wit","year":"2004","journal-title":"Neurology"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nou129","article-title":"Pseudoprogression in patients with glioblastoma: Clinical relevance despite low incidence","volume":"17","author":"Radbruch","year":"2015","journal-title":"Neuro Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2176\/nmc.oa.2020-0308","article-title":"Clinical outcome of cytoreductive surgery prior to bevacizumab for patients with recurrent glioblastoma: A single-center retrospective analysis","volume":"61","author":"Yamaguchi","year":"2021","journal-title":"Neurol Med Chir (Tokyo)"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2020.04.072","article-title":"Impact of early reoperation on the prognosis of patients operated on for glioblastoma","volume":"139","author":"Troya-Castilla","year":"2020","journal-title":"World Neurosurg"},{"key":"B18","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1093\/nop\/npx023","article-title":"Residual enhancing disease after surgery for glioblastoma: Evaluation of practice in the United Kingdom","volume":"5","author":"Ma","year":"2018","journal-title":"Neuro Oncol Pract"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-017-2511-z","article-title":"Early tumor growth between initial resection and radiotherapy of glioblastoma: Incidence and impact on clinical outcomes","volume":"134","author":"Villanueva-Meyer","year":"2017","journal-title":"J Neuro Oncol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23562","article-title":"Incidence of early pseudo-progression in a cohort of Malignant glioma patients treated with chemoirradiation with temozolomide","volume":"113","author":"Taal","year":"2008","journal-title":"Cancer"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-015-1774-5","article-title":"Characterization of pseudoprogression in patients with glioblastoma: Is histology the gold standard","volume":"123","author":"Melguizo-Gavilanes","year":"2015","journal-title":"J Neuro Oncol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-022-04088-3","article-title":"Incidence, molecular characteristics, and imaging features of \"clinically-defined pseudoprogression\" in newly diagnosed glioblastoma treated with chemoradiation","volume":"159","author":"Hagiwara","year":"2022","journal-title":"J Neuro Oncol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1093\/nop\/npad063","article-title":"Incidence and outcome of pseudoprogression after radiation therapy in glioblastoma patients: A cohort study","volume":"11","author":"Blakstad","year":"2024","journal-title":"Neuro Oncol Pract"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.627325","article-title":"Distinguishing pseudoprogression from true early progression in isocitrate dehydrogenase wild-type glioblastoma by interrogating clinical, radiological, and molecular features","volume":"11","author":"Li","year":"2021","journal-title":"Front Oncol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2020.103188","article-title":"Pseudoprogression versus true progression in glioblastoma patients: A multiapproach literature review: Part 1 - Molecular, morphological and clinical features","volume":"157","author":"Le Fevre","year":"2021","journal-title":"Crit Rev Oncol Hematol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3171\/2012.12.JNS12125","article-title":"Postoperative ischemic changes following resection of newly diagnosed and recurrent gliomas and their clinical relevance","volume":"118","author":"Gempt","year":"2013","journal-title":"J Neurosurg"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2003.98.6.1175","article-title":"Perioperative complications and neurological outcomes of first and second craniotomies among patients enrolled in the Glioma Outcome Project","volume":"98","author":"Chang","year":"2003","journal-title":"J Neurosurg"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1007\/s00701-021-05067-9","article-title":"Reducing complication rates for repeat craniotomies in glioma patients: A single-surgeon experience and comparison with the literature","volume":"164","author":"Morshed","year":"2022","journal-title":"Acta Neurochir (Wien)"},{"key":"B29","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1007\/s11060-011-0784-1","article-title":"Risk of ischemia in glioma surgery: Comparison of first and repeat procedures","volume":"107","author":"Dutzmann","year":"2012","journal-title":"J Neuro Oncol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2011.09.025","article-title":"Incidence, risk factors and management of delayed wound dehiscence after craniotomy for tumor resection","volume":"19","author":"Barami","year":"2012","journal-title":"J Clin Neurosci"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s15010-020-01534-0","article-title":"Surgical site infections after glioblastoma surgery: Results of a multicentric retrospective study","volume":"49","author":"Salle","year":"2021","journal-title":"Infection"},{"key":"B32","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1056\/NEJMoa043331","article-title":"Mgmt gene silencing and benefit from temozolomide in glioblastoma","volume":"352","author":"Hegi","year":"2005","journal-title":"N Engl J Med"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noy132","article-title":"Mgmt promoter methylation status testing to guide therapy for glioblastoma: Refining the approach based on emerging evidence and current challenges","volume":"21","author":"Mansouri","year":"2019","journal-title":"Neuro Oncol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1093\/neuros\/nyy049","article-title":"Surgery for glioblastoma in light of molecular markers: Impact of resection and Mgmt promoter methylation in newly diagnosed Idh-1 wild-type glioblastomas","volume":"84","author":"Gessler","year":"2019","journal-title":"Neurosurgery"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1872660\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:26:44Z","timestamp":1788841604000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1872660\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":34,"alternative-id":["10.3389\/fonc.2026.1872660"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1872660","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,8]]},"article-number":"1872660"}}