{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:25:59Z","timestamp":1787199959150,"version":"build-2736575974"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T00:00:00Z","timestamp":1787184000000},"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. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Recurrent or refractory glioblastoma has a poor prognosis, and no universally accepted standard treatment has been established. Randomized evidence is fragmented, making pairwise comparisons insufficient. This study aimed to compare available treatments using a frequentist network meta-analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>PubMed, Web of Science, and the Cochrane Library were searched from inception to April 2026 for randomized controlled trials involving adults with recurrent or refractory glioblastoma. Prespecified outcomes were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Hazard ratios (HRs) were used for PFS and OS, and odds ratios (ORs) for ORR. Random-effects frequentist network meta-analyses were conducted, with P-scores used as exploratory rankings. Sensitivity analyses excluded trials with fewer than 20 patients in any treatment arm. The protocol was registered with PROSPERO (CRD420261398465).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-four studies were included in the qualitative synthesis, of which 19 contributed to at least one network meta-analysis. Compared with lomustine, bevacizumab plus lomustine significantly improved PFS (HR\u202f=\u202f0.57, 95% CI: 0.40\u20130.80), and remained significant after excluding small trials (HR\u202f=\u202f0.58, 95% CI: 0.34\u20130.97). Bevacizumab plus vorinostat had the highest numerical P-score for PFS, although its effect was not statistically significant. No intervention showed a statistically significant OS advantage over bevacizumab. Rindopepimut plus bevacizumab had the most favorable numerical OS estimate (HR\u202f=\u202f0.53, 95% CI: 0.23\u20131.21), but this was non-significant and derived from an EGFRvIII-positive population. No treatment significantly improved ORR versus bevacizumab, whereas nivolumab was associated with lower odds of response (OR\u202f=\u202f0.28, 95% CI: 0.14\u20130.57). Excluding small trials had limited influence on PFS and OS findings but altered the ORR ranking by removing the highly ranked ERC1671-based regimen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Bevacizumab plus lomustine showed the clearest PFS benefit, but the absence of an OS benefit precludes interpretation as broadly superior. No treatment showed a confirmed OS advantage, and the favorable numerical signal for rindopepimut plus bevacizumab should not be generalized beyond EGFRvIII-positive patients. P-score rankings should be considered exploratory and interpreted alongside effect estimates, confidence intervals, sample sizes, molecular eligibility, safety, and treatment burden.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420261398465<\/jats:ext-link>\n                      , Identifier: CRD420261398465.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1896062","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:15:47Z","timestamp":1787199347000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative efficacy of therapeutic strategies for recurrent or refractory glioblastoma: a systematic review and network meta-analysis"],"prefix":"10.3389","volume":"17","author":[{"given":"Hao","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leilei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Medical Ultrasound, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihe","family":"Yun","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianyong","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuming","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangjian","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital","place":["Jinan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1231","DOI":"10.1093\/neuonc\/noab106","article-title":"The 2021 WHO classification of tumors of the central nervous system: a summary","volume":"23","author":"Louis","year":"2021","journal-title":"Neuro-Oncology"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1038\/s41571-020-00447-z","article-title":"EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood","volume":"18","author":"Weller","year":"2021","journal-title":"Nat Rev Clin 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