# Impact of Infection on Survival Outcomes in High-Grade Gliomas: A Retrospective Analysis of 26 Cases in Our Fifteen-Year Experience—Janus Faced Phenomenon

## TL;DR

This study found that infections after brain tumor surgery can sometimes lead to longer survival times, suggesting a complex relationship between infections and outcomes in high-grade glioma patients.

## Contribution

The study is one of the largest to show that surgical site infections may have both harmful and beneficial effects on survival in high-grade glioma patients.

## Key findings

- Infected patients had a higher mean survival time compared to non-infected patients.
- Infections showed a wide variability in survival outcomes, with some patients living much longer.
- IDH mutation status did not explain the improved survival in infected patients.

## Abstract

High-grade gliomas are aggressive brain tumors with poor outcomes, even when treated with surgery, chemotherapy, and radiation. Infections at the site of brain surgery are a known complication, but their effect on survival has been unclear. This study reviewed patients treated between 2010 and 2024 to explore how surgical site infections might influence outcomes. We compared 26 patients who developed infections after surgery to 26 similar patients who did not. Surprisingly, the group with infections showed longer average survival times, although their outcomes varied widely. Some patients with infections lived much longer than expected, while others had shorter survival. In contrast, the patients in non-infected group had similar survival times, but their average survival was shorter. We also found that the bacteria causing the infections varied greatly. A genetic feature commonly linked to better outcomes did not appear to explain the differences in infected patients. This study suggests that infections may have both harmful and potentially helpful effects on survival, depending on timing and other factors. Understanding this unexpected pattern could open new paths for research directions and improved treatment strategies for patients with high-grade gliomas.

Background/Objectives: Glioblastoma IDH-wildtype CNS WHO grade 4 and astrocytoma IDH-mutant WHO grade 4 (together, high-grade gliomas: HGGs) are the most prevalent malignant brain tumors, carrying a poor prognosis despite multimodal treatment. Surgical site infections (SSIs) represent a relative frequent postoperative complication in HGG patients. Despite multimodal treatment protocols combining surgery, radiotherapy, and temozolomide chemotherapy, HGGs remain associated with a dismal prognosis, underscoring the need to evaluate how SSIs impact disease progression and survival outcomes. This study’s aim was to investigate the influence of SSIs on the clinical course of patients with HGGs. Methods: A comprehensive review of medical records for HGG patients treated at our institution between 2010 and 2024 identified 26 patients with SSIs. These patients were compared to an age-matched control group with the same histological diagnosis and treatment regimen. This study analyzed overall survival (OS), microbiological data, and pathological parameters to assess the impact of SSIs on patient outcomes. Survival differences between the infected and non-infected groups were evaluated using Kaplan–Meier survival curves. Remarkably, three patients with exceptionally long overall survival were highlighted in this study. Results: Among the cohort of 2008 patients with HGG surgery, 26 patients developed SSIs. An age-matched control group of 26 patients was identified, none of whom experienced SSIs. Comparing the OS between the infected and uninfected groups, a statistically significant improvement in OS was observed in the infected group (p = 0.049). The median OS in the infected group was 388 days, slightly shorter than the median OS of 422 days in the control group. However, the mean OS was markedly higher in the infected group (674 days) compared to the control group (442 days). The standard deviation of OS in the infected group was notably expansive, indicating substantial variability in survival outcomes. A cluster of infected patients with SSIs near the time of diagnosis had shorter OS, while other infected cases demonstrated significantly longer survival, exceeding both median and mean OS values. In contrast, the uninfected group showed limited standard deviation values, with uniformly distributed individual OS data around the median and mean values. Expectedly, IDH mutation status significantly influenced the survival in cohort patients. However, when stratified by infection status, no association between IDH mutation and improved infection-related survival was identified. The microbiological profile of SSIs was diverse, encompassing Gram-positive and Gram-negative bacteria as well as aerobic and anaerobic organisms. Conclusions: These findings underscore the heterogeneity of infection-related outcomes and their potential impact on survival in HGG patients. According to our knowledge, our study is one of the largest retrospective studies to date investigating and confirming the significant relationship between SSIs and HGG patients’ survival. Our results confirm the Janus Face phenomenon of infections, having both negative and positive effects depending on the context.