Abstract
Patients with glioblastoma have a very poor prognosis despite aggressive therapeutic strategies. Cytomegalovirus has been detected in >90% of glioblastoma tumors. This virus can affect tumor progression and may represent a novel glioblastoma therapy target. We report, here, a retrospective survival analysis of patients with secondary glioblastoma who were treated with the anti-viral drug valganciclovir at Karolinska University Hospital in Stockholm. We performed survival analyses of eight patients with secondary glioblastoma who were treated with a standard dose of valganciclovir as an add-on to second-line therapy after their disease progression to glioblastoma. Thirty-six patients with secondary glioblastoma admitted during the same time period who received similar treatment and care served as contemporary controls. The patients treated with valganciclovir showed an increased median overall survival after progression to glioblastoma compared with controls (19.1 versus 12.7 months, p = 0.0072). This result indicates a potential positive effect of valganciclovir in secondary glioblastoma, which is in agreement with our previous observation that valganciclovir treatment improves the outcomes of patients with newly diagnosed glioblastoma. Larger randomized studies are warranted to prove this hypothesis.
Highlights
Glioblastoma is the most frequent and deadliest form of brain cancer
CMV may, represent a target of therapy in glioblastoma. In support of this statement, we recently reported that 102 patients with newly diagnosed primary glioblastoma treated with the anti-viral drug valganciclovir had a significantly improved overall survival (OS) as compared with 231 contemporary control patients with similar characteristics who were treated at the same institution (24.1 vs. 13.3 months, p < 0.0001) [14]
Second-line chemotherapy was temozolomide for six patients, two received lomustine, and three were treated with bevacizumab
Summary
Glioblastoma is the most frequent and deadliest form of brain cancer. Primary glioblastoma comprises about 90% of cases and originates de novo, while secondary glioblastomas (10%) are considered to arise from less malignant tumor precursors such as a low-grade diffuse astrocytoma or oligodendrioglioma that progresses into a high-grade lesion. Secondary glioblastoma patients are generally younger (mean age, 45–48 years), and their tumors are characterized by TP53 mutations, 1p19q loss and isocitrate dehydrogenase (IDH) mutations, the latter suggested to be present in 70–80% of cases [3]. Among 14 patients with IDH1 or IDH2 mutations, the median OS was reported to be 31 months, as compared to 15 months in 115 patients with IDH1 wild-type primary glioblastoma tumors [4]. Another study found similar higher survival rates in 36 patients with IDH1-mutant tumors—27.1, versus 11.3 months in 371 patients with IDH1 wild-type tumors [5]. Other studies not defining IDH mutation status did not show a higher survival rate for secondary glioblastoma patients as compared to those with primary disease (7.8 or 11 months, respectively) [2,7]. No defined standard treatment exists for these patients, therapeutic interventions seem to be beneficial in patients with secondary glioblastoma, and patients receiving complete tumor resection and adjuvant radio-chemotherapy seem to survive longer [7]
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