Enhancing Optune Therapy With Targeted Craniectomy

Inclusion Criteria:

* Pathological evidence of GBM using WHO classification criteria
* Estimated survival minimum three months
* Supratentorial tumor
* Not a candidate for further radiotherapy
* First disease recurrence in accordance with RANO criteria
* Karnofsky scale score minimum 70
* Ability to comply with Optune therapy
* Tumor characteristics which indicate significant expected benefit from feasible craniotomy or skull remodelling surgery combined with TTFields
* Focal tumor
* Most superficial border of tumor or resection cavity closer than 2 cm from brain surface
* Use of validated anti-conception for female participants in accordance with guidelines provided by the Danish Health and Medicines Authority
* Signed written consent form

Exclusion Criteria:

* Pregnancy or nursing. Fertile female participants will be required to take a validated pregnancy test for evaluation of pregnancy
* Less than four weeks since radiation therapy
* Infratentorial tumor
* Implanted pacemaker, programmable shunt, defibrillator, deep brain stimulator, other implanted devices in the brain, or documented clinically significant arrhythmias.
* Uncontrollable symptomatic epilepsy, refractory to standard medication. Epilepsy will not necessarily contraindicate participation in the trial as this is a common complication to the disease. Eligibility will be determined by the examining physician and investigators in conjunction upon careful consideration of patient safety.
* Contraindications for skull remodelling surgery, e.g. bleeding diathesis or severe infection.
* Significant co-morbidities (within four weeks prior to enrolment)
* Significant liver function impairment - ALT \> 3 times the upper limit of normal
* Total bilirubin \> upper limit of normal
* Significant renal impairment (serum creatinine \> 1.7 mg/dL)
* Coagulopathy (as evidenced by PT or APTT \> 1.5 times control in normal individuals not undergoing anticoagulation)
* Thrombocytopenia (platelet count \< 100x10\^3/μL )
* Anemia (Hb \< 10 g/L)
* Active participation in another clinical treatment trial

Patients will be regarded as participants when they have signed a consent form and have been found suitable for enrolment by the examining physician, in accordance with the abovecriteria. Patients may receive medication depending on their clinical condition and other diseases.