TTFields Plus FET-PET-Guided Stereotactic Radiosurgery Versus TTFields Alone for Recurrent Glioblastoma (Tarrget 2.0)

This study evaluates whether the addition of FET-PET-guided stereotactic radiosurgery (SRS) to Tumor Treating Fields (TTFields) improves survival outcomes in patients with recurrent IDH-wildtype glioblastoma. Patients with recurrent glioblastoma have limited treatment options and poor prognosis. TTFields is a non-invasive antimitotic therapy that has demonstrated efficacy in recurrent glioblastoma. Stereotactic radiosurgery is commonly used in selected patients with recurrent disease; however, treatment efficacy may be limited by the infiltrative nature of glioblastoma and challenges in accurate target delineation. The study hypothesizes that combining TTFields with FET-PET-guided stereotactic radiosurgery will improve one-year overall survival compared with TTFields alone. Participants will be randomized in a 1:1 ratio to receive either TTFields plus stereotactic radiosurgery or TTFields alone.

Inclusion Criteria: * Age ≥18 years * Karnofsky Performance Status ≥70 * Histologically confirmed IDH-wildtype glioblastoma * First, second, or third recurrence * Radiological recurrence according to RANO 2.0 criteria * Prior radiotherapy and temozolomide treatment * At least 6 months since completion of previous radiotherapy * Contrast-enhancing recurrent lesion visible on MRI * Maximum recurrent lesion diameter ≤5 cm * Available molecular profile including IDH and MGMT status * Adequate hematologic, renal, and hepatic function * Written informed consent Exclusion Criteria: * Previous bevacizumab treatment * Planned chemotherapy or targeted therapy after study intervention * Previous stereotactic re-irradiation within the planned treatment field * More than three recurrences * Significant psychiatric disorders * Significant unrelated neurological disease * Implanted pacemaker, defibrillator, deep brain stimulator, or other incompatible electronic device * Pregnancy or breastfeeding * Active intracranial hemorrhage * Uncontrolled hypertension * Severe renal dysfunction * Participation in another interventional study likely to interfere with this study