Impact of removed tumor volume and location on patient outcome in glioblastoma
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Glioblastoma is an aggressive primary brain tumor with devastatingly poor prognosis. Multiple studies have shown the benefit of wider extent of resection (EOR) on patient overall survival (OS) and worsened survival with larger preoperative tumor volumes. However, the concomitant impact of postoperative tumor volume and eloquent location on OS has yet to be fully evaluated. We performed a retrospective chart review of adult patients treated for glioblastoma from January 2006 through December 2011. Adherence to standardized postoperative chemoradiation protocols was used as an inclusion criterion. Detailed volumetric and location analysis was performed on immediate preoperative and immediate postoperative magnetic resonance imaging. Cox proportional hazard modeling approach was employed to explore the modifying effects of EOR and eloquent location after adjusting for various confounders and associated characteristics, such as preoperative tumor volume and demographics. Of the 471 screened patients, 141 were excluded because they did not meet all inclusion criteria. The mean (±SD) age of the remaining 330 patients (60.6% male) was 58.9 ± 12.9 years; the mean preoperative and postoperative Karnofsky performance scores (KPSs) were 76.2 ± 10.3 and 80.0 ± 16.6, respectively. Preoperative tumor volume averaged 33.2 ± 29.0 ml, postoperative residual was 4.0 ± 8.1 ml, and average EOR was 88.6 ± 17.6%. The observed average follow-up was 17.6 ± 15.7 months, and mean OS was 16.7 ± 14.4 months. Survival analysis showed significantly shorter survival for patients with lesions in periventricular (16.8 ± 1.7 vs. 21.5 ± 1.4 mo, p = 0.03), deep nuclei/basal ganglia (11.6 ± 1.7 vs. 20.6 ± 1.2, p = 0.002), and multifocal (12.0 ± 1.4 vs. 21.3 ± 1.3 months, p = 0.0001) locations, but no significant influence on survival was seen for eloquent cortex sites (p = 0.14, range 0.07–0.9 for all individual locations). OS significantly improved with EOR in univariate analysis, averaging 22.3, 19.7, and 13.2 months for >90, 80–90, and 70–80% resection, respectively. Survival was 22.8, 19.0, and 12.7 months for 0, 0–5, and 5–10 ml postoperative residual, respectively. A hazard model showed that larger preoperative tumor volume [hazard ratio (HR) 1.05, 95% CI 1.02–1.07], greater age (HR 1.02, 95% CI 1.01–1.03), multifocality (HR 1.44, 95% CI 1.01–2.04), and deep nuclei/basal ganglia (HR 2.05, CI 1.27–3.3) were the most predictive of poor survival after adjusting for KPS and tumor location. There was a negligible but significant interaction between EOR and preoperative tumor volume (HR 0.9995, 95% CI 0.9993–0.9998), but EOR alone did not correlate with OS after adjusting for other factors. The interaction between EOR and preoperative tumor volume represented tumor volume removed during surgery. In conclusion, EOR alone was not an important predictor of outcome during GBM treatment once preoperative tumor volume, age, and deep nuclei/basal ganglia location were factored. Instead, the interaction between EOR and preoperative volume, representing reduced disease burden, was an important predictor of reducing OS. Removal of tumor from eloquent cortex did not impact postoperative KPS. These results suggest aggressive surgical treatment to reduce postoperative residual while maintaining postoperative KPS may aid patient survival outcomes for a given tumor size and location.
KeywordsGlioblastoma Extent of resection Postoperative residual EOR Overall survival Removed tumor volume
We thank Kristin Kraus, MSc, for her editorial assistance.
This study was not funded by any specific grant.
Compliance with ethical standards
Conflict of interest
Wala Al-Awad, MD, declares that he has no conflict of interest. Michael Karsy, MD, PhD, declares that he has no conflict of interest. Nader Sanai, MD, declares that he has no conflict of interest. Robert Spetzler, MD, declares that he has no conflict of interest. Yue Zhang, PhD, declares that he has no conflict of interest. Yizhe Xu, MS, declares that she has no conflict of interest. Mark A. Mahan, MD, declares that he has no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was handled under an exemption.
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