Resection of malignant brain tumors in eloquent cortical areas: a new multimodal approach combining 5-aminolevulinic acid and intraoperative monitoring.

OBJECT Several studies have revealed that the gross-total resection (GTR) of malignant brain tumors has a significant influence on patient survival. Frequently, however, GTR cannot be achieved because the borders between healthy brain and diseased tissue are blurred in the infiltration zones of malignant brain tumors. Especially in eloquent cortical areas, resection is frequently stopped before total removal is achieved to avoid causing neurological deficits. Interestingly, 5-aminolevulinic acid (5-ALA) has been shown to help visualize tumor tissue intraoperatively and, thus, can significantly improve the possibility of achieving GTR of primary malignant brain tumors. The aim of this study was to go one step further and evaluate the utility and limitations of fluorescence-guided resections of primary malignant brain tumors in eloquent cortical areas in combination with intraoperative monitoring based on multimodal functional imaging data. METHODS Eighteen patients with primary malignant brain tumors in eloquent areas were included in this prospective study. Preoperative neuroradiological examinations included MR imaging with magnetization-prepared rapid gradient echo (MPRAGE), functional MR, and diffusion tensor imaging sequences to visualize functional areas and fiber tracts. Imaging data were analyzed offline, loaded into a neuronavigational system, and used intraoperatively during resections. All patients received 5-ALA 6 hours before surgery. Fluorescence-guided tumor resections were combined with intraoperative monitoring and cortical as well as subcortical stimulation to localize functional areas and fiber tracts during surgery. RESULTS Twenty-five procedures were performed in 18 consecutive patients. In 24% of all surgeries, resection was stopped because a functional area or cortical tract was identified in the resection area or because motor evoked potential amplitudes were reduced in an area where fluorescent tumor cells were still seen intraoperatively. Grosstotal resection could be achieved in 16 (64%) of the surgeries with preservation of all functional areas and fiber tracts. In 2 patients presurgical hemiparesis became accentuated postoperatively, and 1 of these patients also suffered from a new homonymous hemianopia following a second resection. CONCLUSIONS The authors' first results show that tumor resections with 5-ALA in combination with intraoperative cortical stimulation have the advantages of both methods and, thus, provide additional safety for the neurosurgeon during resections of primary malignant brain tumors in eloquent areas. Nonetheless, more cases and additional studies are necessary to further prove the advantages of this multimodal strategy.

[1]  S. Blond,et al.  Prognosis factors of survival time in patients with glioblastoma multiforme: a multivariate analysis of 340 patients , 2007, Acta Neurochirurgica.

[2]  Ettore Lettich,et al.  Cortical stimulation mapping of language cortex by using a verb generation task: effects of learning and comparison to mapping based on object naming. , 2002, Journal of neurosurgery.

[3]  D. Caldiroli,et al.  Prognostic factors for survival in 676 consecutive patients with newly diagnosed primary glioblastoma. , 2008, Neuro-oncology.

[4]  Mitchel S. Berger,et al.  Brain Mapping Techniques to Maximize Resection, Safety, and Seizure Control in Children with Brain Tumors , 1989 .

[5]  Susan M. Chang,et al.  Prognostic factors for survival of patients with glioblastoma: recursive partitioning analysis. , 2004, Neuro-oncology.

[6]  H. Duffau Lessons from brain mapping in surgery for low-grade glioma: insights into associations between tumour and brain plasticity , 2005, The Lancet Neurology.

[7]  H Stepp,et al.  Fluorescence-guided resection of glioblastoma multiforme by using 5-aminolevulinic acid-induced porphyrins: a prospective study in 52 consecutive patients. , 2000, Journal of neurosurgery.

[8]  Hugues Duffau,et al.  Intraoperative cortico–subcortical stimulations in surgery of low-grade gliomas , 2005, Expert review of neurotherapeutics.

[9]  Jan C Buckner,et al.  Factors influencing survival in high-grade gliomas. , 2003, Seminars in oncology.

[10]  R. Mirimanoff,et al.  Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. , 2005, The New England journal of medicine.

[11]  Thomas Pongratz,et al.  ALA and malignant glioma: fluorescence-guided resection and photodynamic treatment. , 2007, Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer.

[12]  H Stepp,et al.  Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-induced porphyrin fluorescence. , 1998, Neurosurgery.

[13]  Veit Rohde,et al.  EXTENT OF RESECTION AND SURVIVAL IN GLIOBLASTOMA MULTIFORME: IDENTIFICATION OF AND ADJUSTMENT FOR BIAS , 2008, Neurosurgery.

[14]  G. Horstmann,et al.  VOLUMETRIC FOLLOW‐UP OF MENINGIOMAS: A QUANTITATIVE METHOD TO EVALUATE TREATMENT OUTCOME OF GAMMA KNIFE RADIOSURGERY , 2007, Neurosurgery.

[15]  G von Campe,et al.  5-aminolevulinic acid induced protoporphyrin IX fluorescence in high-grade glioma surgery: a one-year experience at a single institutuion. , 2008, Swiss medical weekly.

[16]  Elizabeth Eisenhauer,et al.  Nomograms for predicting survival of patients with newly diagnosed glioblastoma: prognostic factor analysis of EORTC and NCIC trial 26981-22981/CE.3. , 2008, The Lancet. Oncology.

[17]  C. Papagno,et al.  INTRAOPERATIVE SUBCORTICAL LANGUAGETRACT MAPPING GUIDES SURGICAL REMOVALOF GLIOMAS INVOLVING SPEECH AREAS , 2007, Neurosurgery.

[18]  I. Nagata,et al.  USEFULNESS OF INTRAOPERATIVE PHOTODYNAMIC DIAGNOSIS USING 5‐AMINOLEVULINIC ACID FOR MENINGIOMAS WITH CRANIAL INVASION: TECHNICAL CASE REPORT , 2008, Neurosurgery.

[19]  F. Zanella,et al.  Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. , 2006, The Lancet. Oncology.

[20]  M. Papadopoulos,et al.  Survival of patients with glioblastoma multiforme has not improved between 1993 and 2004: analysis of 625 cases , 2007, British journal of neurosurgery.