Incorporating genomic signatures into surgical and medical decision-making for elderly glioblastoma patients

Chibawanye I Ene 1, Patrick J Cimino 2, Howard A Fine 3, Eric C Holland 4

Affiliations

PMID: 33002863
DOI: 10.3171/2020.7.FOCUS20418

Abstract

Glioblastoma (GBM) is the most common type of malignant primary brain tumor in adults. It is a uniformly fatal disease (median overall survival 16 months) even with aggressive resection and an adjuvant temozolomide-based chemoradiation regimen. Age remains an independent risk factor for a poor prognosis. Several factors contribute to the dismal outcomes in the elderly population with GBM, including poor baseline health status, differences in underlying genomic alterations, and variability in the surgical and medical management of this subpopulation. The latter arises from a lack of adequate representation of elderly patients in clinical trials, resulting in limited data on the response of this subpopulation to standard treatment. Results from retrospective and some prospective studies have indicated that resection of only contrast-enhancing lesions and administration of hypofractionated radiotherapy in combination with temozolomide are effective strategies for optimizing survival while maintaining baseline quality of life in elderly GBM patients; however, survival remains dismal relative to that in a younger cohort. Here, the authors present historical context for the current strategies used for the multimodal management (surgical and medical) of elderly patients with GBM. Furthermore, they provide insights into elderly GBM patient-specific genomic signatures such as isocitrate dehydrogenase 1/2 (IDH1/2) wildtype status, telomerase reverse transcriptase promoter (TERTp) mutations, and somatic copy number alterations including CDK4/MDM2 coamplification, which are becoming better understood and could be utilized in a clinical trial design and patient stratification to guide the development of more effective adjuvant therapies specifically for elderly GBM patients.

Keywords: BEV = bevacizumab; CNS = central nervous system; EOR = extent of resection; GBM = glioblastoma; GGN = German Glioma Network; GTR = gross-total resection; IDH1/2 = isocitrate dehydrogenase 1/2; MGMT = [6]-methylguanine-DNA methyltransferase; OS = overall survival; PFS = progression-free survival; PR = partial resection; RT = radiation therapy; SCNA = somatic copy number alteration; SRS = stereotactic radiosurgery; STR = subtotal resection; SupTR = supratotal resection; TERTp = telomerase reverse transcriptase promoter; TMZ = temozolomide; VEGF = vascular endothelial growth factor; age; elderly; glioblastoma; gross-total resection; hypofractionated radiation therapy; somatic copy number alterations; supratotal resection; temozolomide.