Efficacy, Outcome, and Safety of Elderly Patients with Glioblastoma in the 5-ALA Era: Single Center Experience of More Than 10 Years

Abstract

Background: In the next decades, the incidence of patients with glioblastoma (GBM) will increase due to the growth of the elderly population. Fluorescence-guided resection using 5-aminolevulinic acid (5-ALA) is widely applied to achieve maximal safe resection of GBM and is identified as a novel intraoperative marker for diagnostic tissue during biopsies. However, detailed analyses of the use of 5-ALA in resections as well as biopsies in a large elderly cohort are still missing. The aim of this study was thus to investigate the efficacy, outcome, and safety of surgically- treated GBM in the 5-ALA era in a large elderly cohort. Methods: All GBM patients aged 65 years or older who underwent neurosurgical intervention between 2007 and 2019 were included. Data on 5-ALA application, intraoperative fluorescence status, and 5-ALA-related side effects were derived from our databank. In the case of resection, the tumor resectability and the extent of resection were determined. Potential prognostic parameters relevant for overall survival were analyzed. Results: 272 GBM patients with a median age of 71 years were included. Intraoperative 5-ALA fluorescence was applied in most neurosurgical procedures (n = 255/272, 88%) and visible fluorescence was detected in most cases (n = 252/255, 99%). In biopsies, 5-ALA was capable of visualizing tumor tissue by visible fluorescence in all but one case (n = 91/92, 99%). 5-ALA administration did not result in any severe side effects. Regarding patient outcome, smaller preoperative tumor volume (<22.75 cm3), gross total resection, single lesions, improved postoperative neurological status, and concomitant radio-chemotherapy showed a significantly longer overall survival. Conclusions: Our data of this large elderly cohort demonstrate the clinical utility and safety of 5-ALA fluorescence in GBM for improved tumor visualization in both resections as well as biopsies. Therefore, we recommend the use of 5-ALA not only in resections, but also in open/stereotactic biopsies to optimize the neurosurgical management of elderly GBM patients.

Toward digital histopathological assessment in surgery for central nervous system tumors using stimulated Raman histology

“…This is of particular relevance in older patients, who constitute a vulnerable population with a higher rate of surgical and anesthesiological complications. 14 Furthermore, precise estimation of a histopathological tumor entity could be markedly accelerated by using the SRH technique, and thus the surgical strategy for tumor resection could be determined at an early stage (for example, rapid intraoperative differentiation of HGG and metastasis). Additionally, SRH allows for rapid investigation of multiple tissue biopsies from the suspected tumor margin after assumed complete tumor resection within a short period of time.…”

Discriminating Glioblastoma from Peritumoral Tissue by a Nanohole Array-Based Optical and Label-Free Biosensor

“…Some authors described key factors that limit the sensitivity of this approach, like low spatial resolution due to the “averaging effect” or poor optical detection for disseminated and sparse cells in tumor margins [ 31 ]. Additionally, although 5-ALA and sodium fluorescence have been described as well-tolerated compounds with a low rate of side effects in high-grade glioma resection surgery [ 34 ], some studies have described mild side effects, such as intraoperative hypotension in a small proportion of patients [ 35 , 36 ], photosensitivity, and allergic reactions.…”

Glioblastoma Therapy: Past, Present and Future

“…Additionally, techniques like evoked potentials, electromyography, and brain mapping in awake patients, under local anesthesia, are used to monitor and preserve language and cognition during resections in critical brain areas [ 272 ]. The use of the amino acid 5-Ala helps to identify tumor volume and areas of neoplastic infiltration through fluorescent visualization, improves PFS, OS, and reduces postoperative neurological damages [ 269 , 273 , 274 , 275 , 276 ]. 5-Ala has also been effectively used in rGB resection, but the risk of false-positive fluorescence for reactive non-tumor tissue is more remarkable in relapse forms, likely due to an altered BBB [ 277 ].…”