Clinical trial NCT01479686: iMRI Guided Resection in Cerebral Glioma Surgery
Official title: 3.0T High-field Intraoperative MRI Guided Extent of Resection in Cerebral Glioma Surgery: a Single Center Prospective Randomized Triple-blind Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Glioma
Keywords: GLIOMA
NEURONAVIGATION
INTERVENTIONAL MRI
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2011-11-24
Enrollment: 321
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Many clinical studies have been reported on iMRI, however, their evidence levels are relatively not as good as what people hope they will be. Based on the available literature, there is, at best, level 2 evidence that iMRI-guided surgery is more effective than conventional neuronavigation-guided surgery.

The investigators aim to do a single center prospective randomized triple-blind controlled clinical trial to assess the effect of 3.0T high-field intraoperative MRI-guided glioma resection on surgical efficiency and progression-free survival of malignant glioma to provide a level 2A evidence for its clinical application.

Detailed description: Since the first introduction of the GE Signa System by the Brigham and Women's Hospital as the world's first intraoperative MRI in 1993, iMRI has been so increasingly applied that it has been one of the most important techniques and concepts in the field of neurosurgery. Many clinical studies have been reported on this respect, however, their evidence levels are relatively not as good as what people hope they will be.Based on the available literature, there is, at best, level 2B evidence that iMRI-guided surgery is more effective than conventional neuronavigation-guided surgery.

Rationale: Intraoperative magnetic resonance imaging (MRI)-guided intracranial surgery, one of whose most frequently reported indications is cerebral glioma surgery, may help update images for navigational systems, providing data on the extent of resection and localization of tumor remnants, and thereby enable intraoperative reliable immediate resection control to eliminate the effect of brain shift on the extent of resection. Intraoperative MRI systems can be divided into low-field intraoperative MRI(0.5T or less) and high-field intraoperative MRI (1.5T or more) according to their various field strengths. The latter enables intraoperative imaging at higher quality and more available imaging modalities but with more cost and equipment requirements.

Purpose: We aim to do a single center prospective randomized triple-blind controlled clinical trial to assess the effect of 3.0T high-field intraoperative MRI-guided glioma resection on surgical efficiency and progression-free survival of malignant glioma. We hypothesize that the use of high-field intraoperative MRI will enable more complete tumor resection than conventional neuronavigation-guided resection,reducing the morbidity and leading to more improved progression-free survival and quality of life in patients with malignant glioma.

Eligibility criteria: Inclusion Criteria:

1. Individuals aged 18-70 years with highly suspected (as assessed by study surgeon), newly diagnosed, untreated malignant glioma (see appendix 1)
2. Individuals with supratentorial gliomas with bodies involving in frontal lobe, temporal lobe, parietal lobe, occipital lobe or insular lobe
3. Individuals with the preoperative assessment that radiological radicality should be achieved
4. Individuals either with or without tumor in eloquent areas (see appendix 2)
5. Karnofsky performance scale 70 or more
6. All patients gave written informed consent.

Appendix 1. Histological types（WHO 2007）:

1. Astrocytic tumours:Pilomyxoid astrocytoma 9425/3 Pleomorphic xanthoastrocytoma 9424/3 Diffuse astrocytoma 9400/3 Fibrillary astrocytoma 9420/3 Gemistocytic astrocytoma 9411/3 Protoplasmic astrocytoma 9410/3 Anaplastic astrocytoma 9401/3 Glioblastoma 9440/3 Giant cell glioblastoma 9441/3 Gliosarcoma 9442/3
2. Oligodendroglial tumours:Oligodendroglioma 9450/3 Anaplastic oligodendroglioma 9451/3
3. Oligoastrocytic tumours:Oligoastrocytoma 9382/3 Anaplastic oligoastrocytoma 9382/3
4. Ependymal tumours:Ependymoma 9391/3 Cellular 9391/3 Papillary 9393/3 Clear cell 9391/3 Tanycytic 9391/3 Anaplastic ependymoma 9392/3

Morphology code of the International Classification of Diseases for Oncology (ICD-O) {614A} and the Systematized Nomenclature of Medicine (http://snomen.org). Behaviour is coded /0 for benign tumours, /3 for malignant tumours and /1 for borderline or uncertain behaviour.

Tumor grade: grade II\~IV according to the latest WHO grading criteria;

Appendix 2. Tumor location in eloquent areas:

located in or close to areas of the dominant-hemisphere that associated with motor or language functions, including:

1. Frontal lobe, which divided into inferior frontal gyrus (BA44-Pars opercularis, BA45-Pars triangularis/Broca's area), middle frontal gyrus (BA9, BA46), superior frontal gyrus (BA4, BA6, BA8), primary motor cortex (BA4), premotor cortex (BA6), and supplementary motor area (BA6)
2. Parietal lobe, which divided into inferior parietal lobule (BA40-supramarginal gyrus, BA39-angular gyrus), parietal operculum (BA43), and primary somatosensory cortex (BA1, BA2, BA3)
3. Temporal lobe, which divided into transverse temporal gyrus (BA41, BA42), superior temporal gyrus (BA38, BA22/Wernicke's area), middle temporal gyrus (BA21)
4. Insular lobe.

Exclusion Criteria:

1. Individuals with age \< 18 years or \> 70 years
2. Tumours of the midline, basal ganglia, cerebellum, or brain stem
3. Recurrent gliomas after surgery (except needle biopsy)
4. Primary gliomas with history of radiotherapy or chemotherapy
5. Contraindications precluding intraoperative MRI-guided surgery
6. Inability to give informed consent
7. KPS \< 70
8. Renal insufficiency or hepatic insufficiency
9. History of malignant tumours at any body site
10. Tumour locations (in important eloquent area) do not enable complete resection of tumour.

Primary outcomes:
measure: Extent of resection
timeFrame: 3 years
Secondary outcomes:
measure: OS
timeFrame: 10 years
measure: PFS
timeFrame: 10 years
measure: Postoperative complications
timeFrame: after surgery
measure: Health economics
timeFrame: after surgery
measure: MRI-related adverse events
timeFrame: after surgery
measure: Surgery related morbidity
timeFrame: 3 years
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Neurologic Surgery, Huashan Hospital, Shanghai Medical College, Fudan University
state: Shanghai
Study officials:
affiliation: Huashan Hospital
name: Liang-fu Zhou, M.D.
role: STUDY_CHAIR
affiliation: Huashan Hospital
name: Ying Mao, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Huashan Hospital
name: Jin-song Wu, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fountain DM, Bryant A, Barone DG, Waqar M, Hart MG, Bulbeck H, Kernohan A, Watts C, Jenkinson MD. Intraoperative imaging technology to maximise extent of resection for glioma: a network meta-analysis. Cochrane Database Syst Rev. 2021 Jan 4;1(1):CD013630. doi: 10.1002/14651858.CD013630.pub2.