Clinical and prognostic implications of rim restriction following glioma surgery

Clinical and demographic data

Between 2013 and 2017, 468 patients underwent either surgical resection or biopsy at our center, of these 120 for LGG and 348 for GBM. Fourty-four cases of biopsy procedures alone (5 of LGG and 39 of GBM), as well as 23 patients who had no complete pre-and postoperative MRI data (4 of LGG and 19 of GBM), and 80 patients who had no detailed admission, surgery, and discharge or follow-up reports (29 of LGG and 51 of GBM) were excluded from the study. Nineteen LGG and 30 GBM patients who sustained an intraoperative stroke were also excluded. Our final cohort consisted of 272 patients (63 LGG and 209 GBM) who underwent resection and had full datasets that included a long-term clinical evaluation and no evidence of intra-operative stroke.

The combined population mean age at surgery was 53 ± 16 years, with LGG patients being significantly younger than those with GBM (37 ± 12 and 58 ± 14, respectively, p = 0.001). Of the combined study population, 102 (38%) were females with similar rates within each tumor study group. There were 100 (37%) awake operations and 92 (34%) recurrent operations. There was a significantly higher rate of temporal tumors among GBM patients (33% vs 11%, p = 0.001), while insular tumors were more common among LGG patients (21% Vs 9%, p = 0.013). Median preoperative KPS was significantly higher among LGG patients than in GBM (90, 70–100 vs 80, 30–100, p = 0.001). While pre-operative tumor volume was similar (34 ± 32 ml in LGG and 33 ± 25 ml in GBM, p = 0.750), EOR was significantly higher in the GBM group (96 ± 8%) vs 87 ± 11% in the LGG group (p = 0.001).

Incidence and risk factors

Rim restriction was demonstrated on the postoperative DWI studies of 68 patients (25%), including 20 LGG and 48 GBM patients.

We did not find significant differences in the rate of post-op rim restriction between LGG and GBM patients (32% vs 23%, p = 0.184).

We found no significant association between postoperative rim restriction and the evidence of blood in the surgical cavity that was demonstrated on the postoperative CT of 30% of the restriction cases and 28% of the non-restricted ones in LGG (p = 0.864), as well as 51% of GBM patients with restriction vs 49% in those without restriction (p = 0.177).

A univariate analysis that compared patients with and without rim restriction with respect to demographic, clinical, and pathological parameters showed no significant differences between those with and without rim-restriction in the combined GBM + LGG cohort (Table 1). Among GBM patients, rim restriction was more common in tumors located in the temporal lobes (32% Vs 18% in non-temporal areas, p = 0.025) and non-significantly more common in LGG of insular location (54% vs. 24%, p = 0.09). The calculated risk (odds ratio, OR) for post-op rim restriction among temporal GBM cases was 1.74 (95% CI 1.09–4.10, p = 0.027).

Table 1 Clinical and demographic data of patients with and without post-operative rim-restriction on diffusion-weighted imaging, including the entire study population (n = 272), low-grade glioma subgroup (n = 63) and high-grade glioma subgroup (n = 209).


Full IOM of MEPs, anesthesiology and awake monitoring reports were available in 152, 267 and 98 of the combined study population (n = 272), respectively. Neither MEPs changes nor awake intraoperative monitoring parameters showed any significant associations with rim restriction. Duration of anesthesia in the combined GBM and LGG cohort was significantly longer among patients with rim restriction, when compared to those without it (306 ± 87 min and 276 ± 81 min, respectively, P = 0.009). The difference was even more pronounced in the LGG group analysis (375 ± 17 min vs 316 ± 13 min; p = 0.008), Table 2.

Table 2 Correlations between post-op rim restriction on diffusion-weighted imaging and intraoperative parameters in the entire study population, high-grade glioma subgroup and low-grade glioma subgroup: intraoperative monitoring, awake surgery monitoring and anesthesiology parameters (univariate analysis).

Clinical, functional, and cognitive outcomes

Overall and progression-free survival

The mean overall survival time in the LGG group was 56 months (95% confidence interval 52–60), and there was no perioperative mortality. There was no difference in survival between those with and without post-op restriction (p = 0.117). Mean progression free survival (PFS) in the entire LGG group was 44 months (95% CI 37–50) with no significant differences between the subgroups (p = 0.449).

Mean overall survival in the entire GBM group was 22 months (95% confidence interval 19–25). Interestingly, patients with immediate post-op restriction had a non-significant trend towards increased survival (26 months, 95% CI 19–32) as compared to those without (20 months, CI 95% 17–24, p = 0.076). Mean PFS in the GBM group was 13 months (95% CI 10–15) with a non-significant trend towards longer period among patients with immediate post-op restriction (15, 95% CI 19–21), as compared to those without rim restriction (11 months, 95% CI 8–14, p = 0.065).

Motor deficits

New or worsening immediate post-op motor deficits among LGG occurred in 4/20 (20%) of those with post-op restriction, similar to the rate in the non-restriction group (10/43 ,23%, p = 0.772). The rates were 9/48 (19%) in patients with post-op rim restriction and 19/161 (12%) of those without restriction (p = 0.215) in the GBM sub-population. In either group, no significant changes were noted in the rate of motor deficits over time, Tables 3 and 4.

Table 3 Clinical outcomes in low-grade glioma (LGG) patients with (n = 20) and without post-operative rim restriction on diffusion weighted imaging up to 1 year after surgery (n = 43).
Table 4 Clinical outcomes in glioblastoma patients with (n = 48) and without post-operative rim-restriction on diffusion-weighted imaging (n = 161) up to 6 months after surgery.

Speech deficits

Speech deficits were analyzed in a subgroup of patients that underwent surgeries for tumors located in the dominant hemispheres (33 LGG and 103 GBM patients). We found a significantly higher rate of LGG patients with speech deficits in the post-op follow-up period in the restriction group, as compared to the non-restriction group (p = 0.004). All rim-restriction cases with speech deficits (n = 7) involved eloquent areas: either the left frontal, temporal or insular lobes. The percentage of patients with speech deficits in the post-op period decreased from 63 to 46% in the restriction group (p = 0.873) and from 18 to 9% (p = 0.989) in the non-restriction group after 1 year of follow-up, Table 3. Among GBM patients, no significant differences were noted in the rate of speech deficits in the post-op follow-up period between the restriction and non-restriction groups (p = 0.226), Table 4.

Functional assessment scores (KPS, MRS and cognitive tests)

We did not detect any significant differences in the KPS and MRS scores in either the LGG or GBM populations during our follow-up period (p > 0.05, see Tables 3 and 4).

Cognitive function tests, as previously described11, were performed in 33 LGG patients before and 3 months after surgery. We compared the results of 6 patients with post-op rim restriction and 27 with no restriction and could not detect any significant differences between the 2 groups in any of the functions assessed. Pre- and post-operative global cognitive scores were 98 ± 11and 95 ± 9 in the restriction group, and 95 ± 9 and 95 ± 9 in the non-restriction group, respectively (p = 0.194).

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