The RECMAP-study: Resection With or Without Intraoperative Mapping for Recurrent Glioblastoma: Study Protocol for An International Multicenter Prospective Cohort Study (ENCRAM 2301)
The RECMAP-study: Resection With or Without Intraoperative Mapping for Recurrent Glioblastoma: Study Protocol for An International Multicenter Prospective Cohort Study (ENCRAM 2301)
Resection of glioblastoma in or near functional brain tissue is challenging because of the proximity of important structures to the tumor site. To pursue maximal resection in a safe manner, mapping methods have been developed to test for motor and language function during the operation. Previous evidence suggests that these techniques are beneficial for maximum safe resection in newly diagnosed grade 2-4 astrocytoma, grade 2-3 oligodendroglioma, and recently, glioblastoma. However, their effects in recurrent glioblastoma are still poorly understood. The aim of this study, therefore, is to compare the effects of awake mapping and asleep mapping with no mapping in resections for recurrent glioblastoma.
This study is an international, multicenter, prospective 3-arm cohort study of observational nature. Recurrent glioblastoma patients will be operated with mapping or no mapping techniques with a 1:1 ratio. Primary endpoints are: 1) proportion of patients with NIHSS (National Institute of Health Stroke Scale) deterioration at 6 weeks, 3 months, and 6 months after surgery and 2) residual tumor volume of the contrast-enhancing and non-contrast-enhancing part as assessed by a neuroradiologist on postoperative contrast MRI scans. Secondary endpoints are: 1) overall survival (OS), 2) progression-free survival (PFS), 4) health-related quality of life (HRQoL) at 6 weeks, 3 months, and 6 months after surgery, and 4) frequency and severity of Serious Adverse Events (SAEs) in each arm. Estimated total duration of the study is 5 years. Patient inclusion is 4 years, follow-up is 1 year.
The study will be carried out by the centers affiliated with the European and North American Consortium and Registry for Intraoperative Mapping (ENCRAM).
This is an international, multicenter, prospective, 3-arm cohort study. Eligible patients are operated with or without mapping techniques with a 1:1 ratio with a sequential computer-generated random number as subject ID. Patients with motor-eloquent tumors will be treated in all study arms, while speech-eloquent tumors will only be treated in either the awake mapping or no mapping arm. The RECMAP study is similar to the SAFE-trial24 (awake craniotomy versus craniotomy under general anesthesia for glioblastoma patients, NCT03861299) and is initiated by the same center, however, the presented study will be different in various ways: the RECMAP study (1) will be an observational, prospective cohort study, (2) will include asleep mapping as an additional treatment arm, (3) will evaluate the extent of resection of the non-contrast-enhancing part of the tumor as well, (4) only includes recurrent tumors (5) will include neurosurgical centers in the United States and is part of the ENCRAM Research Consortium18. The RECMAP study is also similar to the PROGRAM study25 (awake mapping versus asleep mapping versus no mapping for high-grade glioma patients, NCT04708171), with the difference that the RECMAP study includes recurrent tumors (while the PROGRAM study includes newly diagnosed tumors), and that the RECMAP study includes recurrent glioblastoma, while the PRGORAM study includes WHO grade 3 and 4 gliomas.
Study patients are operated with either awake mapping, asleep mapping or no mapping and will undergo evaluation at presentation (baseline) and during the follow-up period at 6 weeks, 3 months, and 6 months postoperatively. Motor function will be evaluated using the NIHSS (National Institute of Health Stroke Scale) and MRC (Medical Research Council) scales. Language function will be evaluated using a standard neurolinguistic test-battery consisting of the Aphasia Bedside Check (ABC), Shortened Token test, Verbal fluency, Picture description and Object naming. This neurolinguistic test-battery is the result of a consensus between the participating centers. Cognitive function will be assessed using the Montreal Cognitive Assessment (MOCA). Overall patient functioning with be assessed with the Karnofsky Performance Scale (KPS) and the ASA (American Society of Anesthesiologists) physical status classification system for comorbidities. Health-related quality of life (HRQoL) will be assessed with the EQ-5D questionnaire and the EORTC QLQ-C30 and EORTC QLQ-BN20 questionnaires. Overall survival and progression-free survival will be assessed. We expect to complete patient inclusion in 4 years. The estimated duration of the study, including follow-up, will be 5 years.
The primary study objective is to evaluate the safety and efficacy of resections with or without mapping techniques (neurological morbidity and residual CE and NCE tumor volume) in recurrent glioblastoma patients as expressed by NIHSS scores and volumetric data. Secondary study objectives are to study the overall survival (OS), progressive-free survival (PFS), health-related quality of life (HRQoL), and Serious Adverse Events (SAEs) after resections with or without mapping techniques as expressed by survival data, progression on follow up MRI scans based on the RANO criteria26 for tumor progression, quality of life questionnaires (EORTC QLQ C30, EORTC QLQ BN20, EQ-5D), and registration of SAEs.
Patients will be recruited from the neurosurgical or neurological outpatient clinic or through referral from general hospitals of the participating neurosurgical hospitals, located in Europe and the United States. The study is carried out by centers from the ENCRAM Consortium.
Inclusion Criteria:
Exclusion Criteria:
j.gerritsen@erasmusmc.nl+31107036130
a.vincent@erasmusmc.nl+31107034211
San Francisco, California 94143, United States