In this retrospective monocentric cohort of 47 patients ≥ 65 year-old and harboring an IDH-wildtype glioblastoma, we show that: 1) gross total resection was feasible with low complication rates, even in frail patients ; 2) surgical treatment, age, sex, preoperative KPS and the 5-mFI score did not independently influence surgical-related mortality and morbidity; 3) gross total resection was an independent predictor of a KPS score increase ≥ 10 points postoperatively; 4) gross total resection and age ≤ 70 were independent predictors of a longer overall survival; 5) sex, 5-mFI, postoperative complications, and preoperative KPS status did not independently influence overall survival.
The role of frailty on general surgery outcomes has been widely reported and is associated with higher complication and reoperation rates, longer hospital stay, loss of independence, higher readmission rates, and mortality [16–21]. Concerning neurosurgery, only few studies assessed the postoperative outcomes of frail patients, and even fewer studies focused on glioblastoma patients [22, 22–24]. The present results, focused on IDH-wildtype glioblastoma patients ≥ 65-year-old, suggest that the extent of resection remains a strong predictor of longer overall survival and better functional outcomes, even in frail patients. Indeed, gross total resection was feasible despite frailty and was an independent predictor of KPS score increase postoperatively. These results suggest that an aggressive resection using required intraoperative tools to maximize the safety of procedure could be proposed in frail IDH-wildtype glioblastomas patients ≥ 65-year-old.
In the present series, the 5-mFI score was not a predictor of both survival and functional outcomes (p < 0.05). These results differ from previous reports [2, 3, 11, 22–24]. These differences should be related to several aspects. First, our study focused on patient harboring a IDH-wildtype glioblastoma while previous studies included a wider but more heterogeneous population, including all brain tumors. Second, the score used to evaluate the frailty varied. Several authors reported an equally effectiveness of mFI-5 compared to the mFI-11 to predict surgical outcomes [22, 25, 26]. Here, we decided to adopt the 5-mFI score, which was easier to adopt in clinical practice than conventional 11-item modified frailty index. Bonney et al. used the Johns Hopkins Adjusted Clinical Groups (JHACG) to prove the role of frailty as independent predictive factors for a poor outcome following brain tumor surgery. They found an association between frailty and postoperative outcomes, including surgical complications, mental status changes, pulmonary insufficiency, and venous thromboembolism and also longer lengths of stay . However, any distinction between benign or malignant tumor, such as between primary or secondary, lesions was performed. Cloney et al. included only glioblastoma patients and used the mFI-11 score . They found that an increased frailty is directly related to higher morbidity and mortality rates. However, authors decided to include the frailty score as a factor addressing the choose of surgical treatment (resection versus biopsy). Consequentially, frail patients were preferentially addressed to biopsy, thereby affecting the surgical efficacy. Similar results are reported also by Krenzlin and colleagues . They retrospectively reviewed data of 104 patients aged > 70 years harboring a glioblastoma and used the G8 Questionnaire and the 15-item Groningen Frailty Index to estimate frailty. They observed that frail patients had a shorter overall survival than not-frail patients (median overall survival of 7.1 months vs 14.3 months; p = 0.0025) and a higher postoperative complication rate (OR 3.913, 95%CI 1.0515–14.5620, p = 0.0419). However, the German group used the 15-item Groningen Frailty Index combined to the G8 Questionnaire to estimate frailty, resulting a more comprehensive but articulate and complex score to use in clinical practice. Zouaoui et al. retrospectively analyzed 265 elderly patients with glioblastoma . They suggested that patients aged > 70 years have a survival benefit with increasing treatment: the reported median survival for untreated patients was 2.0 months vs 8.8 months and 12.2 months in those treated by surgery plus radiotherapy and comprehensive multi-modality treatment, respectively.
Gross total resection still remains the strongest predictor of better survival and functional outcome in old patients harboring a IDH-wildtype glioblastoma, despite frailty, therefore an overall preoperative evaluation should be considered for a better risk stratification.
This real-life practice series evaluates the efficacy and safety of the surgical management of IDH-wildtype glioblastoma in frail patients ≥ 65-year-old. In previous studies, the evaluation of frailty score impacted the surgical treatment decision making. The present study controlled for this bias by analyzing all patients whatever their 5-mFI score. This cohort reflects the real-life surgical management of aged and frail patient harboring an IDH-wildtype glioblastoma and could help: 1) envision a particular surgical technique based on clinical requirements without increasing complications rates and envision the surgery despite frailty score; 2) identify preoperatively cases at risk of poor clinical outcomes postoperatively by evaluating age, performance status and comorbidities through easy and clinically feasible scores.
These findings should be interpretated with caution, given the retrospective and monocentric design, the exploratory design of statistical analyses, the lack of control group and the lack of an external validation set, all limiting the generalizability of the results. In addition, the low number of patients limited the number of predictive variables to be entered in multivariable models. Further confirmatory analyses are required.