Literature ReviewManagement of Glioblastoma Multiforme in Elderly Patients: A Review of the Literature
Introduction
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults and occurs most commonly in individuals older than 65 years of age.1 This aggressive, quickly fatal disease has a median survival of approximately 14 months, but only after maximal therapy of resection, chemotherapy (ChT), and radiotherapy (RT).2 The universally poor prognosis of GBM is compounded with increasing age, as elderly patients have markedly worse outcomes than younger patients, with median survival ranging between 4 and 9 months.3, 4, 5, 6, 7 The standard of care for GBM includes maximal safe resection with adjuvant RT and concomitant temozolomide (TMZ).8 However, the clinical trials that guided these treatment recommendations specifically excluded elderly patients, and thus their efficacy in the elderly may not be applicable.9 Furthermore, elderly patients are more likely to be treated conservatively due to fear of treatment toxicity, increased complication rates, and inability to tolerate extensive procedures.4, 5, 6, 7, 10, 11
Although age is a confounder of mortality in patients with GBM, there may be other factors contributing to poor outcomes. The “baby boomer” generation continues to grow in number, and thus it is important to identify therapeutic approaches to improve survival in this often-forgotten patient population. This review aims to highlight the current literature on surgical and medical management of GBM in elderly patients, including our own experience, and to provide rational treatment approaches for frequently debated situations.
Section snippets
Extent of Resection in Elderly Patients with GBM
Several studies, including randomized clinical trials, have demonstrated the survival benefit of maximum safe resection as first-line treatment of GBM.12, 13, 14, 15, 16, 17, 18, 19 Although there is some debate between the optimal percent of tumor bulk removed and postoperative residual tumor volume, there is no debate that greater extent of resection is associated with improved survival in patients of all ages, including elderly patients. Oszvald et al.11 performed a subset analysis of 146
RT or TMZ for GBM in Elderly Patients
In the International Atomic Energy Agency Randomized Phase III study, Roa et al.23 investigated whether a short 1-week RT regimen could be a treatment option for elderly or frail patients with newly diagnosed GBM.24 Frail patients were defined as ≥50 years old with a KPS of 50%–70%; elderly and frail patients were defined as ≥65 years old with a KPS of 50%–70%; and elderly patients were defined as ≥65 years old with a KPS of 80%–100%.23 A total of 98 patients were included in this study and
RT with Concomitant TMZ for Elderly Patients with GBM
Adjuvant RT and concomitant TMZ is the standard of care for patients with GBM after histologic assessment of neurosurgical resection or biopsy specimen and, with the recent updates of the WHO guidelines, the mutational status of isocitrate dehydrogenase (IDH).28 However, elderly patients often are not provided standard of care, given their increased risk of treatment toxicity, high complication rate, and overall vulnerability, including greater probability of comorbid conditions. This leads to
Recurrent GBM in Elderly Patients
Although many avenues for treatment of primary GBM in the elderly have been explored, studies investigating treatment of recurrent GBMs in this population are scarce. Generally, in these patients, best supportive care usually is pursued, given the poor prognosis and the risk of compromised quality of life. Socha et al.39 studied data from the International Atomic Energy Agency trial23 and identified 84 elderly and/or frail patients who had recurrence of their primary disease. A total of 41 of
Molecular Considerations in GBM
The World Health Organization's 2016 classification of central nervous system tumors introduces a paradigm shift in glioma classification and relies on molecular markers to diagnose and define subtypes of glioma, including GBM.28, 43 With this new classification system, GBMs can be either IDH-mutant or IDH-wild type, with the former having a less-aggressive although still uniformly fatal clinical course. However, this does not bring any changes to the practice of treating elderly patients with
Conclusions
Currently, there is no established standard of care for elderly patients with GBM; however, significant data show there are treatment options available that not only improve OS, but also do not necessarily compromise quality of life. It has been demonstrated in several studies that when possible, the neurosurgeon should aim for GTR of tumor in elderly patients, regardless of age; if GTR is not possible, STR results in improved OS compared with those patients who undergo operative biopsy alone
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Cited by (14)
First validation of the G-8 geriatric screening tool in older patients with glioblastoma
2019, Journal of Geriatric OncologyCitation Excerpt :The definition of “older patients” remains problematic, because it varied among studies validating the G8 scale, and among different studies in general (with the cut-off ranging from 65 to 70 years) [14]. Sixty-five years was used as the threshold in one previous review, taking into account the epidemiology of cancer [23]. Since the publication of the 2005 International Society of Geriatric Oncology guidelines (SIOG) [6], various screening tools have been devised, among which only five were developed specifically for older cancer populations.
Glioblastoma Survival Outcomes at a Tertiary Hospital in Appalachia: Factors Impacting the Survival of Patients Following Implementation of the Stupp Protocol
2018, World NeurosurgeryCitation Excerpt :The low overall median survival of our patient population may be explained by the fact that most of the patients were >60 years old at the time of diagnosis (Table 1). Our finding of low median and 1-year survival in the elderly group corroborates other studies, which also found a low median survival of 4–6 months in this population, sometimes even with standard treatment.17,18 In such cases, attention shifts toward maintaining a good quality of life.
Reactive oxygen species in plasma medical science (PAM and cancer therapy)
2018, Plasma Medical ScienceGlioblastoma: Biology, diagnosis, and treatment
2018, Encyclopedia of CancerBrain metastases in the elderly – Impact of residual tumor volume on overall survival
2023, Frontiers in OncologyPalliative care of older glioblastoma patients in neurosurgery
2022, Journal of Neuro-Oncology
Conflict of interest statement: The authors declare that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.