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Institutet","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/056d84691","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Emerging evidence suggests that antiviral treatment targeting human cytomegalovirus (HCMV) may improve outcomes in patients with glioblastoma (GBM). In this study, we analyzed serological data from the placebo-controlled VIGAS1 trial (Eudra number 2006-002022-29), which assessed the effect of valganciclovir (VGCV) on GBM progression in 42 patients, for impact of VGCV in preventing HCMV reactivation. Methods: VIGAS1 patients had undergone radical surgery and were randomized to receive either VGCV (n = 22) or placebo (n = 20) alongside standard radiochemotherapy. Blood was prospectively collected at baseline and 3-, 12- and 24-week follow-up visits. GBM cell lines and a cytomegalovirus-infected murine brain cancer model were used to validate the clinical findings. Results: Over the 24-week study period, we found that HCMV reactivation, as inferred from IgM seropositivity, occurred in 58.3% of patients in the placebo group, whereas this was completely prevented in the VGCV-treated group except for one patient with no treatment compliance (p = 0.0005). HCMV reactivation was linked to early recurrence. IgG-positive patients treated with VGCV showed a significantly longer time to progression (TTP) than those receiving placebo (6.7 vs. 3.7 months, p = 0.0408). We found a significant association between higher steroid doses and enhanced reactivation in the placebo group. In vitro and murine studies confirmed that corticosteroids, combined with radiation therapy, enhanced cytomegalovirus reactivation, which was mitigated by antiviral treatment. Conclusions: These findings suggest that preventing HCMV reactivation with antiviral therapy may improve patient outcomes, especially in HCMV-seropositive GBM patients, and further support the hypothesis that HCMV is a tumor-promoting virus.<\/jats:p>","DOI":"10.3390\/cancers18101575","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T16:04:36Z","timestamp":1778601876000},"page":"1575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Valganciclovir Therapy Prevents Human Cytomegalovirus Reactivation in Glioblastoma Patients Undergoing Radiochemotherapy and Extends Time to Tumor Progression"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2706-4683","authenticated-orcid":false,"given":"Mattia Russel","family":"Pantalone","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Karolinska University Hospital, 17177 Stockholm, Sweden"},{"name":"Department of Medicine, Karolinska Institute, 17164 Stockholm, Sweden"},{"name":"Department of Neurosurgery, Link\u00f6ping University Hospital, 58185 Link\u00f6ping, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1968-6447","authenticated-orcid":false,"given":"Giuseppe","family":"Stragliotto","sequence":"additional","affiliation":[{"name":"Department of Neurology, Karolinska University Hospital, 17177 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerea","family":"Martin-Almazan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Karolinska Institute, 17164 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inti","family":"Peredo-Harvey","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Karolinska University Hospital, 17177 Stockholm, Sweden"},{"name":"Department of Medicine, Karolinska Institute, 17164 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge L.","family":"Jimenez-Macias","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA"},{"name":"Legorreta Cancer Center, Brown University, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1158-2512","authenticated-orcid":false,"given":"Afsar","family":"Rahbar","sequence":"additional","affiliation":[{"name":"Department of Medicine, Karolinska Institute, 17164 Stockholm, Sweden"},{"name":"Department of Neurology, Karolinska University Hospital, 17177 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Lawler","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Warren Alpert Medical School, Brown University, Providence, RI 02903, USA"},{"name":"Legorreta Cancer Center, Brown University, Providence, RI 02903, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiri","family":"Bartek","sequence":"additional","affiliation":[{"name":"Danish Cancer Society Research Center, 2100 Copenhagen, Denmark"},{"name":"Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Science for Life Laboratory, Karolinska Institute, 17165 Stockholm, Sweden"},{"name":"Institute of Molecular Genetics, The Czech Academy of Sciences, 142 20 Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8955-3610","authenticated-orcid":false,"given":"Cecilia","family":"S\u00f6derberg-Naucler","sequence":"additional","affiliation":[{"name":"Department of Medicine, Karolinska Institute, 17164 Stockholm, Sweden"},{"name":"Department of Biosciences, InFLAMES Research Flagship Center, MediCity, University of Turku, 20520 Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N. 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