Long-Term Survival in IDH-Wild-Type Glioblastoma: Clinical and Molecular Insights From Two Exceptional Cases

Glioblastoma is the most common and aggressive primary malignant brain tumor in adults, associated with poor prognosis despite standard multimodal treatment. Long-term survival beyond five years is rare, particularly in IDH-wild-type disease. We report the cases of two female patients with IDH-wild-type, CNS WHO grade 4 glioblastoma who achieved survival exceeding five years following standard therapy. The first case was a 51-year-old woman presenting with seizures and a left temporoparietal glioblastoma. She underwent gross total resection followed by radiotherapy (60 Gy) with concurrent and 12 cycles of adjuvant temozolomide (200 mg/m²). Due to high PD-L1 expression, nivolumab was added during adjuvant treatment. Molecular analysis revealed PTEN, TP53, and TERT promoter mutations. She remains disease-free at five years. The second case involved a 27-year-old woman presenting with headache and a left frontal glioblastoma. She underwent gross total resection followed by standard chemoradiotherapy and 12 cycles of adjuvant temozolomide (200 mg/m²). Next-generation sequencing (NGS) identified multiple alterations in DNA damage response and tumor suppressor pathways. She also remains in complete remission at five years. These cases highlight that long-term survival in IDH-wild-type glioblastoma is possible, although rare. Favorable clinical factors such as young age, good performance status, and gross total resection, together with distinct molecular profiles, may contribute to prolonged survival. These observations underscore the importance of integrating clinical and molecular features to refine prognostic assessment in glioblastoma.