{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T03:36:46Z","timestamp":1788838606265,"version":"build-2803163510"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100012990","name":"Universit\u00e0 degli Studi di Siena","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012990","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurooncol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults, with a median overall survival (OS) rarely exceeding 15 months despite multimodal therapy. While established prognostic factors include age, Karnofsky Performance Status (KPS), and molecular features such as MGMT promoter methylation and IDH mutation status, increasing attention has focused on the role of treatment timing as a potentially modifiable prognostic determinant. In particular, Overall Treatment Time (OTT)\u2014the number of calendar days from the first to the last radiotherapy fraction\u2014may impact survival by enabling tumor repopulation when extended or interrupted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective monocentric cohort study of 166 consecutive adult patients with histologically confirmed IDH-wild-type glioblastoma treated with standard concurrent chemoradiotherapy and adjuvant temozolomide between January 2016 and January 2024. OTT was defined as the total number of days from radiotherapy start to end, including all interruptions. A cutoff of 48 days was adopted based on prior evidence. Patients were stratified according to OTT, number and cause of radiotherapy interruptions, and molecular status (MGMT promoter methylation and EGFR amplification). The primary endpoints were OS and progression-free survival (PFS), analyzed with Kaplan\u2013Meier and Cox regression models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Median OTT was 43 days (range: 40\u201365). Patients with OTT\u2009\u2264\u200948 days had a significantly longer median OS than those with OTT\u2009&gt;\u200948 days (20 vs. 10 months,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003). Multivariable Cox regression confirmed OTT\u2009&gt;\u200948 days as an independent negative prognostic factor (HR\u2009=\u20091.41,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009). Multiple interruptions, regardless of cause, further reduced OS, particularly in patients with MGMT-methylated tumors and low EGFR expression. Clinical interruptions\u2014often due to toxicity\u2014were associated with significantly worse outcomes than single technical interruptions. Notably, the negative impact of prolonged OTT was significantly more pronounced in the MGMT-methylated subgroup (p for interaction\u2009=\u20090.018), suggesting a biologically distinct vulnerability to treatment delays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study demonstrates that prolonged OTT and radiotherapy interruptions are independently associated with inferior survival in patients with IDH-wild-type glioblastoma, particularly in biologically favorable subgroups such as MGMT-methylated tumors. These findings underscore the importance of strict adherence to treatment schedules and minimizing avoidable delays. Molecular profiling may aid in identifying patients most vulnerable to the adverse effects of treatment prolongation, supporting a more personalized and time-sensitive approach to GBM management. Further prospective validation is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11060-025-05215-6","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T08:21:48Z","timestamp":1758788508000},"page":"1261-1269","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Timing matters: overall treatment time, radiotherapy interruptions, and outcomes in glioblastomas\u2014prognostic significance in different biological sub-groups"],"prefix":"10.1007","volume":"175","author":[{"given":"Paolo","family":"Tini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio","family":"Donnini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Marampon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierpaolo","family":"Pastina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Rubino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Battaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Chibbaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Cerase","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Antonietta","family":"Mazzei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isacco","family":"Desideri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Minniti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"issue":"10","key":"5215_CR1","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1056\/NEJMoa043330","volume":"352","author":"R Stupp","year":"2005","unstructured":"Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. 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All patients provided informed consent for treatment and inclusion of their anonymized data in research analyses.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}