Establishing percent resection and residual volume thresholds affecting survival and recurrence for patients with newly diagnosed intracranial glioblastoma

Abstract

Introduction: Surgery is first-line therapy for glioblastoma, and there is evidence that gross total resection is associated with improved survival. Gross total resection, however, is not always possible, and relationships among extent (percent) of resection (EOR), residual volume (RV), and survival are unknown. The goals were to evaluate whether there is an association between EOR and RV with survival and recurrence and to establish minimum EOR and maximum RV thresholds.

Methods: Adult patients who underwent primary glioblastoma surgery from 2007 to 2011 were retrospectively reviewed. Three-dimensional volumetric tumor measurements were made. Multivariate proportional hazards regression analysis was used to evaluate the relationship between EOR and RV with survival and recurrence.

Results: Of 259 patients, 203 (78%) died and 156 (60%) had tumor recurrence. The median survival and progression-free survival were 13.4 and 8.9 months, respectively. The median (interquartile range) pre- and postoperative tumor volumes were 32.2 (14.0-56.3) and 2.1 (0.0-7.9) cm(3), respectively. EOR was independently associated with survival (hazard ratio [HR], 0.995; 95% confidence interval [CI]: 0.990-0.998; P = .008) and recurrence (HR [95% CI], 0.992 [0.983-0.998], P = .005). The minimum EOR threshold for survival (P = .0006) and recurrence (P = .005) was 70%. RV was also associated with survival (HR [95% CI], 1.019 [1.006-1.030], P = .004) and recurrence (HR [95% CI], 1.024 [1.001-1.044], P = .03). The maximum RV threshold for survival (P = .01) and recurrence (P = .01) was 5 cm(3).

Conclusion: This study shows for the first time that both EOR and RV are significantly associated with survival and recurrence, where the thresholds are 70% and 5 cm(3), respectively. These findings may help guide surgical and adjuvant therapies aimed at optimizing outcomes for glioblastoma patients.

Keywords: GBM; extent of resection; glioblastoma; residual; surgery; survival; volumetric.

Figures

Fig. 1.

Schematic diagram of the patients included and the methodology used in the study. There were a total of 508 patients who underwent intracranial GB surgery at a single tertiary care institution from 2007 to 2011. Of these 508 patients, 259 who underwent nonbiopsy surgical resection of a primary or newly diagnosed GB were included in the study. The goals of the study were to identify whether there was an association between increasing percent resection and decreased residual volume with survival and recurrence and to establish a minimum percent resection and maximum residual volume threshold.

Fig. 2.

Volumetric measurements. The pre- and postoperative MRIs were obtained and reviewed for each patient. All patients underwent axial MRI with gadolinium at 1.5- to 3-mm intervals on the day prior to or on the day of surgery and within 48 h of surgery. Using OsiriX software, the area of contrast enhancement was measured for each axial section, and tumor volume was quantified based on the sum of axial areas in a semiautomated manner.

Fig. 3.

Survival and recurrence for all included patients who underwent nonbiopsy surgery of a newly diagnosed intracranial GB from 2007 to 2011 at a single tertiary care institution. (A) Survival of all patients. The median survival for all included patients was 13.4 months. The 6-, 12-, 18-, and 24-month overall survival rates were 79.0%, 58.9%, 32.9%, and 19.3%, respectively. (B) Recurrence of all patients. The median PFS of all included patients was 8.9 months. The 6-, 12-, 18-, and 24-month PFS rates were 73.3%, 29.7%, 14.3%, and 6.6%, respectively.

Fig. 4.

Survival and recurrence by percent tumor resection. (A) Survival by percent resection. The median survival for patients with >70% tumor resection was 14.4 months compared with 10.5 months for patients with ≤70% resection (P = .0003). The 6-, 12-, and 24-month overall survival rates for patients with >70% tumor resection were 83.3.3%, 64.7%, and 20.3.5%, respectively. In comparison, the 6-, 12-, and 24-month overall survival rates for patients with ≤70% tumor resection were 65.5%, 38.7%, and 15.5%, respectively. (B) PFS by percent resection. The median PFS for patients with >70% tumor resection was 9.0 months compared with 7.1 months for patients with ≤70% resection (P = .01). The 6-, 12-, and 24-month PFS rates for patients with >70% tumor resection were 76.5%, 33.6%, and 7.6%, respectively. In comparison, the 6-, 12-, and 24-month overall survival rates for patients with ≤70% tumor resection were 61.0%, 13.8%, and 3.4%, respectively.

Fig. 5.

Survival and recurrence by residual tumor volume. (A) Survival by residual tumor volume. The median survival for patients with 3 of residual tumor volume was 15.3 months compared with 11.6 months for patients with ≥5 cm3 of residual volume (P = .001). The 6-, 12-, and 24-month overall survival rates for patients with <5 cm3 of residual tumor volume were 84.1%, 64.5%, and 21.2%, respectively. In comparison, the 6-, 12-, and 24-month overall survival rates for patients with ≥5 cm3 of residual tumor volume were 68.8%, 46.2%, and 15.2%, respectively. (B) Recurrence by residual volume. The median PFS for patients with <5 cm3 RV was 9.2 months compared with 7.5 months for patients with ≥5 cm3 RV (P = .005). The 6-, 12-, and 24-month PFS rates for patients with <5 cm3 RV were 75.7%, 31.8%, and 6.6%, respectively. In comparison, the 6-, 12-, and 24-month overall survival rates for patients with ≥5 cm3 RV were 67.2%, 14.3%, and 0.0%, respectively.