Surgery for Recurrent Glioblastoma

Summary

Patients with glioblastoma face a grim prognosis. Despite recent advancement in neurosurgical technology and neuro-oncology glioblastomas almost invariably progress or recur after a median of 4-8 months. The strategy to repeat tumor resection at recurrence in order to minimize tumor load and thus to facilitate subsequent second-line therapy has been shown to be feasible and safe. However, evidence for a survival benefit of surgery for recurrent glioblastoma is scarce and relies entirely on retrospective analyses. While most retrospective analyses report an apparent survival benefit, an EORTC meta-analysis on second-line therapies found no survival difference in patients with or without surgery at recurrence. With regard to the risks and costs inherent to surgery for glioblastoma, a randomized controlled trial is required. The purpose of the study is to compare the effect of craniotomy and tumor resection followed by adjuvant second-line therapy to no surgery followed by second-line therapy on overall survival, neurological status, and quality of life. Analysis of overall survival will be used to improve sample size estimation of a subsequent phase III trial for craniotomy and tumor resection of glioblastoma recurrence in cooperation with the EORTC.

Interventions

• Surgery followed by adjuvant second-line therapy · PROCEDURE

  Surgery: Surgery must take place between day 1 and 14 after study inclusion and within 21 days from the MRI on which recurrence was diagnosed. The modalities of surgery and the choice of pre- and intra-operative technical adjuncts is at the treating neurosurgery discretion. Surgery must take place between day 1 and 14 after study inclusion and within 21 days from the MRI on which recurrence was diagnosed. The modalities of surgery and the choice of pre- and intra-operative technical adjuncts is at the treating neurosurgery discretion. However, some form of intra-operative resection control (iMRI or intra-operative fluorescence) and function control (electrophysiology) should be available to the surgeon and used when warranted. Adjuvant second-line therapy: Patients will be seen after surgery by the treating neurooncologist. Modalities of adjuvant second-line therapy are individually defined according to local guidelines and are not stipulated by study protocol.

• Second-line therapy alone · PROCEDURE

  Patients randomized to the non-surgical cohort receive second-line therapy according to local guidelines. Modalities thereof are not stipulated by study protocol.

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

Inclusion Criteria:

* Written informed consent
* ≥18 years of age
* Prior resection of glioblastoma confirmed by histology
* Glioblastoma pretreated with standard radiotherapy without or with temozolomide
* First progression according to RANO criteria
* First progression not within 3 months after completion of radiation therapy
* Complete removal of contrast-enhancing lesion considered feasible without significant risk of permanent speech or motor function according to MRI as confirmed by study eligibility committee after screening and prior to recruitment
* No encroachment of the M1 or A1 segments of the medial and anterior cerebral artery on MRI
* No contrast enhancement in presumed speech and primary motor areas on MRI
* No midline shift on MRI
* No contrast enhancing ventricular spread, multifocal recurrence, meningeosis carcinomatosa or infiltration of the contra-lateral hemisphere on MRI
* No contra-indication for surgery
* Good functional status (KPS ≥ 70)

Exclusion Criteria

Sites (25)

• Universitätsklinikum Innsbruck, Innsbruck, Austria · RECRUITING
• Johannes Kepler University Linz University, Clinic for Neurosurgery, Linz, Austria · RECRUITING
• Medical University of Vienna, Department of Neurosurgery, Vienna, Austria · RECRUITING
• Centre Hospitalier Universitaire Dijon Bourgogne, Department of Neurosurgery, Dijon, France · RECRUITING
• Hospices Civils de Lyon - CHU de Lyon, Department of Neuro-Oncology, Lyon, France · RECRUITING
• Assistance Publique - Hôpitaux de Marseille, Department of Neuro-Oncology, Marseille, France · RECRUITING
• Centre Hospitalier Universitaire de Nice, Department of Neurosurgery, Nice, France · RECRUITING
• Assistance Publique - Hôpitaux de Paris (AP-HP), Department of Neurosurgery, Paris, France · RECRUITING
• Centre Hospitalier Universitaire de Saint-Étienne, Department of Neurosurgery, Saint-Etienne, France · RECRUITING
• Institut de Cancérologie Strasbourg Europe (ICANS), Department of Oncology, Strasbourg, France · RECRUITING
• Centre Hospitalier Régional et Universitaire de Tours (CHRU Tours), Department of Neurosurgery, Tours, France · RECRUITING
• Helios Klinikum Erfurt, Erfurt, Germany · RECRUITING
• Universitätsklinikum Münster, Münster, Germany · RECRUITING
• Department of Neurosurgery, Hospital of Larissa & General Hospital of Larissa, Larissa, Greece · RECRUITING
• Department of Neurosurgery, Amsterdam University Medical Center, Amsterdam, Netherlands · RECRUITING
• Department of Neurosurgery, Radboud University Medical Center, Nijmegen, Nijmegen, Netherlands · RECRUITING
• Department of Neurosurgery, Haaglanden Medical Center, The Hague, The Hague, Netherlands · RECRUITING
• Department of Neurosurgery, Centro Hospitalar Universitário Lisboa Norte - Hospital de Santa Maria, Lisbon, Portugal · RECRUITING
• Department of Neurosurgery, L'Hospitalet de Llobregat, Barcelona, Barcelona, Spain · RECRUITING
• University of Gothenburg, Department of Clinical Neuroscience, Gothenburg, Sweden · NOT_YET_RECRUITING
• University Hospital of Umeå, Department of Diagnostics and Intervention, Umeå, Sweden · NOT_YET_RECRUITING
• Universitätsspital Basel, Basel, Switzerland · RECRUITING
• Dep. of Neurosurgery, Bern University Hospital, Bern, Switzerland · RECRUITING
• Dep. of Neurosurgery, Centre hospitalier universitaire vaudois, Lausanne, Switzerland · RECRUITING
• Ospedale Regionale di Lugano, Lugano, Switzerland · RECRUITING