Napady padaczki związane z guzem w momencie rozpoznania glejaków multifokalnych wskazują na zapalny profil molekularny i wiążą się z lepszym rokowaniem przeżycia
Tumor-associated epilepsy at diagnosis in glioblastoma patients reveals an inflammatory molecular signature and is associated with better overall survival
W skrócie
Badanie wykazało, że pacjenci z glejakami (agresywnymi nowotworami mózgu) u których pojawiły się napady padaczki w momencie rozpoznania choroby mają lepsze szanse na przeżycie - około 4-5 miesięcy dłużej niż ci bez napadów. Okazało się, że u tych pacjentów tumor ma inny charakter molekularny, z większym stanem zapalnym, a całkowite chirurgiczne usunięcie guza daje im szczególnie duże korzyści. Wyniki sugerują, że informacja o napadach padaczki u pacjenta może być ważnym znakiem prognostycznym przy planowaniu leczenia glejaków.
Oryginalny abstract (angielski)
BACKGROUND: Glioblastoma (GB) is the most aggressive primary brain tumor in adults. Tumor-associated epilepsy at diagnosis (TAE) is common, yet its prognostic significance remains unclear. METHODS: We analyzed a retrospective multicenter test cohort of 855 GB patients (Aachen, Hamburg, Bielefeld) and validated findings in a prospectively collected cohort of 344 patients (Erlangen). Survival was assessed using multivariable Cox regression, propensity score matching, and interaction modeling of TAE and extent of resection (EOR). Molecular profiling included methylation-based classification, epigenetic deconvolution, and spatial transcriptomics. RESULTS: TAE was independently associated with improved survival (HR 0.81, 95% CI 0.69-0.99, P = .036, absolute survival advantage ∼4-5 months). This effect was validated in the independent cohort (C-index 0.68 (95% CI 0.62-0.74) and persisted in propensity-matched analyses (HR 0.74, 95% CI 0.56-0.96, P = .027). Interaction modeling revealed that gross total resection (GTR) improved survival in both groups but particularly in patients with TAE (EOR interaction HR 0.69, 95% CI 0.49-0.99, P = .041). In this subgroup, partial resection provided no significant advantage over biopsy, whereas patients without seizures benefited incrementally from both partial resection and GTR. Molecular analysis demonstrated enrichment of the RTK II subtype, differentiated cell states, and an inflammatory microenvironment in glioblastoma with TAE; tumors without seizures displayed neuronal and stem-like features. Functional validation using Electrogenomics showed that glioblastoma cortical slices with increased inflammatory score exhibited synchronization of action potentials characteristic for seizure-like epileptiform activity. CONCLUSIONS: TAE at diagnosis is a favorable prognostic marker in GB, defining a biologically distinct subgroup. Seizure status modifies the prognostic effect of surgical resection, underscoring the importance of GTR particularly in patients presenting with TAE.