- Department of Neurosurgery, Uttar Pradesh University of Medical Sciences, Saifai,
- Department of Neurosurgery, Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Hanuman Prasad Prajapati, Department of Neurosurgery, Uttar Pradesh University of Medical Sciences, Saifai, Uttar Pradesh, India.
DOI:10.25259/SNI_552_2022Copyright: © 2022 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Hanuman Prasad Prajapati1, Deepak Kumar Singh2. Recurrent glioblastoma in elderly: Options and decision for the treatment. 02-Sep-2022;13:397
How to cite this URL: Hanuman Prasad Prajapati1, Deepak Kumar Singh2. Recurrent glioblastoma in elderly: Options and decision for the treatment. 02-Sep-2022;13:397. Available from: https://surgicalneurologyint.com/surgicalint-articles/11845/
Background: Glioblastoma (GBM) is the most common primary malignant brain tumor in adult. Its incidence increases with age and nearly half of the all newly diagnosed GBM cases are older than 65 years. Management of GBM in elderly is challenging and recurrence poses further challenge. This article aims to review the literature, evaluate the various options, and to decide the treatment plan in elderly cases with GBM recurrence.
Methods: A systemic search was performed with the phrase “recurrent GBM (rGBM) in elderly and management” as a search term in PubMed central, Medline, and Embase databases to identify all the articles published on the subject till February 2022. The review included peer-reviewed original articles, review articles, clinical trials, and keywords in title and abstract.
Results: Out of 473 articles searched, 15 studies followed our inclusion criteria and were included in this review. In 15 studies, ten were original and five were review articles. The minimum age group included in these studies was ≥65 years. Out of 15 studies, eight studies had described the role of resurgery, four chemotherapy, three resurgery and/or chemotherapy, and only one study on role of reradiotherapy in patients with rGBM. Out of eight studies described the role of resurgery, six have mentioned improved survival and two have no survival advantage of resurgery in cases of rGBM.
Conclusion: Resurgery is the main treatment option in selected elderly rGBM cases in good performance status. In patients with poor performance status, chemotherapy has better post progression survival than best supportive care.
Keywords: Elderly, Glioblastoma, Recurrent, Treatment
Glioblastoma (GBM) is the most common primary malignant brain tumor in adult. The current median age is 64 years.[
While the current standard of care for younger patients includes surgical resection followed by concurrent chemoradiation and adjuvant chemotherapy with temozolomide (TMZ),[
Several studies show the benefit from active treatment for newly diagnosed GBM in elderly[
The review was designed in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analysis.
Articles published in PubMed central, Medline, and Embase data bases till March 2022 were all searched. In relevant literature, references were manually searched for additional articles. We screened the title and abstract by combining the term (“recurrent” [All Fields] AND (“GBM” [MeSH Terms] OR “GBM” [All Fields]) AND (“aged” [MeSH Terms] OR “aged” [All Fields] OR “elderly” [All Fields]) AND (“therapy” [Subheading] OR “therapy” [All Fields] OR “treatment” [All Fields] OR “therapeutics” [MeSH Terms] OR “therapeutics” [All Fields]).
Only nonexperimental and nonanimal clinical studies were included in the study. Articles written only in English language were considered. We have included only those published articles on elderly rGBM, in which patients were managed previously by surgery and postoperative chemoradiotherapy before recurrence, while excluding those articles in which GBM cases were managed either with surgery or radiotherapy.
Median overall survival (OS) (in weeks), progression free survival (PFS) (in weeks), and post progression survival (PPS) (in weeks) were the values collected. These variables were defined as the median time of intervention to death as median OS and to clinical or radiological evidence of tumor recurrence/progression as median PFS. PPS is defined as the time from tumor progression to death after the treatment.
Results of literature search were imported to EndNote X9 (Clarivate Analytics, Philadelphia, Pennsylvania). Software utilization sought to reduce data entry errors and bias (i.e., duplicating references). All investigation reports were reviewed to assess for in consistencies (e.g., design description, outcome presentation, and total patients analyzed).
Data work entered in Microsoft Office Excel 2007 and analyzed using SPSS version 24.0 (IBM Corp.; Chicago, United states. Data were analyzed at two levels, descriptive and analytical. Frequency, percentage, range, means, and median were used to describe the characteristics of study participants. P < 0.05 was considered statistically significant.
Out of 473 articles searched, 15 studies followed our inclusion criteria and were included in this study [
In 15 studies, ten were original and five were review articles. The minimum age group included in these studies was ≥65 years. Out of 15 studies, eight studies had described the role of re-surgery, four chemotherapy, three resurgery and/or chemotherapy, and only one study on role of reradiotherapy in patients with rGBM. Out of eight studies described the role of resurgery, six had mentioned improved survival and two had no benefit of resurgery in cases of rGBM. Three studies had mentioned the role of TMZ rechallenge, three fotemustine (FTM), one lomustine, and one on the role of bevacizumab (BEV) [
Management of elderly patients with GBM is difficult due to the poor prognosis, multiple comorbidities, and an increased risk of adverse effects from radiotherapy.[
Age, although associated with comorbidities and overall frailty, does not necessarily reflect the patients physiologic reserve or functional capacity[
(A) Elderly rGBM patients in good performance status (KPS ≥70%).
In these cases, local treatment (surgery and/or radiotherapy) results in better survival.
Resurgery versus conservative
The decision for resurgery after recurrence should be individualized as it is associated with greater morbidity and mortality.[
Nuñez et al.[
Chen et al.[
Resurgery versus chemotherapy
Resurgery had more survival benefits as compare to systemic therapy (chemotherapy) in rGBM in elderly patients with good KPS. A Korean study had evaluated the outcome of various salvage strategies in rGBM patients after upfront maximum debulking surgery followed by chemoradiotherapy and adjuvant TMZ, median PPS was 13.2 months after resurgery versus 5.6 months after TMZ chemotherapy.[
Resurgery versus reradiotherapy
Elderly rGBM cases managed with resurgery had better survival benefit as compare to reradiotherapy. On analyzing the previous literature, it is found that patients managed with resurgery (51 weeks, 95% CI 28.9–73.1 weeks) have better median PPS as compare to patients given only re-RT (17 weeks, 95% CI 12.2–21.8 weeks), P = 0.62.[
(B) Elderly rGBM patients in poor performance status (KPS<70%)
Chemotherapy versus local treatment
Local treatment (resurgery) results in improved survival benefit in rGBM in elderly patients with good KPS score, but it is associated with poor outcome in patients with poor KPS score (KPS <70%) probably due to postoperative complications. In this special subgroup, chemotherapy seems to be optimal therapeutic approach.
Zanello et al.[
After multiple adjustment using cox models, poor KPS from recurrence was independently associated with shorter OS from recurrence (aHR, 1.52 [95% CI: 1.27–1.82], P < 0.001). On reviewing the literature, patients treated with chemotherapy had better median PPS (21 weeks, 95% CI 8.8–33.2) as compare to patients treated with local treatment (14 weeks, 95% CI 0.9–46.7) P = 0.88.[
Best supportive care (BSC) versus any treatment
Elderly rGBM patients with poor KPS need not be automatically precluded from salvage treatment. Instead, the treatment should be individually tailored based on the presenting symptoms and the patient specific needs and goals. Some previous study[
BEV may be most beneficial for patients with more robustly enhancing tumors that are associated with substantial cerebral edema. This therapeutic agent is associated with improved PPS and radiographic response rate, which are secondary in part to its mechanism of action of decreasing cerebral edema and normalizing the tumor vasculature.[
The newer treatment modalities such as molecular targeted therapy, immunotherapy, tumor treating fields, photodynamic therapy, intraoperative radiotherapy, laser interstitial thermal therapy, nuclear medicine thermal therapy, chimeric antigen receptor T-cell therapy, and various combination therapy have been investigated in elderly patients with newly diagnosed GBM cases but not in recurrent cases. At present, there is no evidence to support the role of these newer treatments outside the clinical trials, particularly for elderly cases. Further randomized control trials are required to validate efficacy and safety of these newer treatments and to analyze the role of molecular markers such as IDH mutant status, EGFR amplification, and MGMT methylation status to prognosticate these patients.
Management of elderly rGBM depends on the extent of the disease and performance status of the patients. Resurgery has better OS than other modalities of treatment and should be considered in selected elderly rGBM patients with good performance status. It has comparable complication rates as in nonelderly rGBM cases. Chemotherapy has better survival than BSC in elderly rGBM cases with poor performance status. Role of reradiotherapy and other newer treatments require further evaluation in well-designed, randomized, and control trials.
Patient’s consent not required as there are no patients in this study.
Publication of this article was made possible by the James I. and Carolyn R. Ausman Educational Foundation.
There are no conflicts of interest.
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