Association of perioperative adverse events with subsequent therapy and overall survival in patients with WHO grade III and IV gliomas

Abstract

Background: Maximum safe resection followed by chemoradiotherapy as current standard of care for WHO grade III and IV gliomas can be influenced by the occurrence of perioperative adverse events (AE). The aim of this study was to determine the association of AE with the timing and choice of subsequent treatments as well as with overall survival (OS).

Methods: Prospectively collected data of 283 adult patients undergoing surgery for WHO grade III and IV gliomas at the University Hospital Zurich between January 2013 and June 2017 were analyzed. We assessed basic patient characteristics, KPS, extent of resection, and WHO grade, and we classified AE as well as modality, timing of subsequent treatment (delay, interruption, or non-initiation), and OS.

Results: In 117 patients (41%), an AE was documented between surgery and the 3-month follow-up. There was a significant association of AE with an increased time to initiation of subsequent therapy (p = 0.005) and a higher rate of interruption (p < 0.001) or non-initiation (p < 0.001). AE grades correlated with time to initiation of subsequent therapy (p = 0.038). AEs were associated with shorter OS in univariate analysis (p < 0.001).

Conclusion: AEs are associated with delayed and/or altered subsequent therapy and can therefore limit OS. These data emphasize the importance of safety within the maximum-safe-resection concept.

Keywords: adverse events; complications; glioblastoma; high grade glioma; maximum-safe-resection; neurosurgery; subsequent therapy; treatment delay.

Figure 1

CDG grade, KPS, and subsequent therapy (A): Of all 252 cases with any subsequent therapy, in 75 cases an AE prior to beginning of subsequent therapy was noted. The time to initiation and the CDG grade were correlated with Spearman’s rho = 0.13 (p = 0.038). The linear fit has a slope of 3.9 days per increment of CDG. (B): The occurrence of AE until 3 months postoperatively is associated with a significantly lower OS in Log Rank test (p < 0.001) (C): The occurrence of altered subsequent therapy is associated with a significantly lower OS in log-rank test (p < 0.001) (D): The subgroups with interruption or non-initiation of subsequent therapy had both a significant decreased OS (p < 0.001). The subgroup with delay showed no significant association with OS (p = 0.113).

Figure 2

CDG grade and KPS. Over all 283 patients, in 78 patients at least one AE occurred before discharge. KPS and CDG at discharge were correlated with Spearman’s rho = -0.41 (p < 0.001). The linear fit had a slope of -9.5 KPS points per increment of CDG.