Methodological Considerations in Elderly Brain Tumor Surgery

A recent letter to the editor published in the Egyptian Journal of Neurosurgery has raised significant methodological concerns regarding a study by Hussain et al. that evaluated morbidity and mortality following brain tumor surgery in elderly patients. The original article, published on 30 June 2026, presented a prospective cohort with detailed multivariate analysis of mortality predictors. However, the correspondence argues that the statistical framework used in the original study contains critical weaknesses that limit the precision and generalizability of its findings. The letter commends the authors for addressing an important and underexplored area of geriatric neurosurgery.

The primary criticism focuses on the multivariate logistic regression model employed in the original study. The letter notes that the model included five predictor variables in a cohort that contained only 22 non-survivors. This results in fewer than five events per variable, a ratio that is well below the commonly recommended threshold of ten events per variable. In statistical practice, falling below this threshold can lead to regression coefficients that become unstable and biased. The authors of the letter point to the wide confidence intervals reported in the original study as evidence of this instability. For instance, the adjusted odds ratio for an ASA score of 3 or higher was reported as 5.12, with a 95% confidence interval ranging from 1.15 to 22.84. Such a broad range limits the precision of these estimates and suggests that the findings may not be robust enough for generalization to other populations.

A second major concern relates to the composition of the patient cohort. The original study combined markedly heterogeneous tumor pathologies within a single analysis of brain tumor surgery. The cohort included tumor pathologies ranging from benign meningiomas to glioblastoma multiforme. Prior systematic reviews have demonstrated that outcomes after meningioma resection in the elderly follow a distinct risk profile compared to that of malignant glioma surgery. By pooling these diverse pathologies, the apparent effects of age, ASA score, or Karnofsky Performance Status on mortality in the present study may partly reflect diagnosis-specific risks rather than a generalizable age-related surgical risk.

The letter also addresses the inherent selection bias present in the surgical cohort. All included patients had already been deemed suitable operative candidates by a multidisciplinary team before being enrolled in the study. This pre-selection process means that the cohort does not represent the broader population of elderly patients presenting with brain tumors. This includes elderly patients managed conservatively or with radiosurgery. While the authors of the original study acknowledge this limitation, the letter emphasizes that it has significant implications for the external validity of the findings.

Furthermore, the choice of a 90-day mortality endpoint is questioned in the context of glioblastoma patients. The letter argues that this timeframe may not adequately capture the long-term outcomes for this specific group. Even with optimal multimodal therapy, which includes surgery, radiotherapy, and concomitant temozolomide, median survival in the glioblastoma population typically extends well beyond 90 days. The authors of the letter suggest that diagnosis-stratified analyses or a longer follow-up period would provide a more complete and accurate picture of the true surgical benefit across this heterogeneous population.

The correspondence concludes by congratulating the original authors for their contribution to this important field. The letter suggests that future research should focus on multicenter studies with larger sample sizes. Longer follow-up periods are also recommended. Additionally, the authors advocate for more diagnosis-stratified analyses. These methodological improvements would help further validate risk-prediction models for elderly patients receiving brain tumor surgery.

Subject of Research: Morbidity and mortality in elderly brain tumor surgery: methodological considerations

Article Title: Morbidity and mortality in elderly brain tumor surgery: methodological considerations

Article References: Hanchate, A. A., Karim, A., Ullah, F. M., Jabbar, D., & Khan, M. (2026). Morbidity and mortality in elderly brain tumor surgery: methodological considerations. Egyptian Journal of Neurosurgery, 41(1), Article 144. https://doi.org/10.1186/s41984-026-00649-0

Image Credits: AI Generated

DOI: 10.1186/s41984-026-00649-0

Keywords: Morbidity, mortality, elderly, brain, tumor, surgery, methodological, considerations, scientific research