Patient clinical characteristics
One hundred twenty-five patients (mean age, 41.7 years; 79 men) were enrolled in this study (Table 1). Of these, 58 (46.4%) were younger than 40 years, and 67 (53.6%) were older than 40 years. The median follow-up time was 529 days (range, 142–1382). Up to the final follow-up date, 113 patients (90.4%) died and 12 patients (9.6%) were still alive. Additionally, 72 patients (57.6%) underwent GTR and 53 patients (42.4%) underwent STR. Moreover, there were 33 patients (26.4%) in group R, 39 patients (31.2%) in group F, 23 patients (18.4%) in group E, and 30 patients (24.0%) in group O (Fig. 1).
Table 1
Demographic and clinical characteristics of the study population
Characteristics | Number of patients |
Gender | |
Male | 79 |
Female | 46 |
Age | |
Mean age ± SEM (years old) | 41.7 ± 0.75 |
< 40 years old | 58 |
≥ 40 years old | 67 |
Extent of resection | |
Total | 72 |
Subtotal | 53 |
Pathological Diagnosis (primary operation) | |
Astrocytoma | 43 |
Anaplastic Astrocytoma | 11 |
Oligodendrocytoma | 25 |
Anaplastic Oligodendrocytoma | 15 |
Lower grade but unknown detailed pathology | 31 |
Pathological Diagnosis (secondary operation) | |
GBM-O (include oligodendrocyte) | 16 |
GBM | 109 |
Newly occurring functional impairments | |
Health | 86 |
Neurological impairments | 39 |
Newly occurring epileptic seizure | |
Epileptic seizure | 23 |
Non-epileptic seizure | 102 |
Diagnosis status | |
Without newly occurring symptoms | 33 |
With newly occurring symptoms | 92 |
Preoperative KPS score (secondary operation) | |
100 | 15 |
90 ~ 100 (< 100) | 27 |
80 ~ 90 (< 90) | 34 |
70 ~ 80 (< 80) | 49 |
Postoperative KPS score (secondary operation) | |
90 ~ 100 (≤ 100) | 14 |
80 ~ 90 (< 90) | 26 |
70 ~ 80 (< 80) | 41 |
60 ~ 70 (< 70) | 24 |
50 ~ 60 (< 60) | 20 |
※ KPS = Karnofsky Performance Status |
According to the WHO 2007 criteria, the patients’ primary histopathology included astrocytoma (43/125, 34.4%), anaplastic astrocytoma (11/125, 8.8%), oligodendrocytoma (25/125, 20.0%), and anaplastic oligodendrocytoma (15/125, 12.0%). Thirty-one patients (31/125, 24.8%) had low-grade gliomas with unknown detailed pathology.
KPS scores were evaluated before and after the second tumor resection. The preoperative KPS scores were categorized as 70 ~ 80 (< 80), 80 ~ 90 (< 90), 90 ~ 100 (< 100), and 100, with 49, 34, 27, and 15 patients in each group, respectively. Similarly, the postoperative KPS scores were categorized as 50 ~ 60 (< 60), 60 ~ 70 (< 70), 70 ~ 80 (< 80), 80 ~ 90 (< 90), 90 ~ 100 (< 100), and 100, with 20, 24, 41, 26, and 14 patients in each group, respectively.
Prognostic factors for OS in all patients
OS data after the second tumor resection were available for all patients. The median OS of all patients was 301 days (10.0 months) and the mean OS was 400 days (13.3 months). Univariate Cox regression analysis showed that male sex (hazard ratio (HR), 0.678; 95% confidence interval (CI), 0.461–0.997; p = 0.048), GTR (HR, 0.464; 95% CI, 0.317–0.678; p < 0.0001), diagnosis without newly occurring symptoms on follow-up (HR, 0.474; 95% CI, 0.306–0.733; p = 0.0006), high preoperative KPS score (HR, 0.975; 95% CI, 0.958–0.993; p = 0.005), high postoperative KPS score (HR, 0.971; 95% CI, 0.956–0.987; p = 0.0004), and isocitrate dehydrogenase (IDH) mutation (HR, 0.572; 95% CI, 0.385–0.851; p = 0.006) were favorable prognostic factors for OS (Table 2).
Table 2
Univariate and multivariate analysis of secondary OS in all sGBM patients
| Univariate analysis | Multivariate analysis |
HR (95.0% CI) | p value | HR (95.0% CI) | p value |
Gender (male) | 0.678 (0.461 to 0.997) | 0.048 | 0.748 (0.495 to 1.130) | 0.168 |
Age | 0.992 (0.971 to 1.014) | 0.492 | - | - |
Extent of resection (gross total resection) | 0.464 (0.317 to 0.678) | < 0.0001 | 0.613 (0.408 to 0.923) | 0.019 |
Diagnosed sGBM without newly occurring symptoms | 0.474 (0.306 to 0.733) | 0.0006 | 0.481 (0.308 to 0.750) | 0.001 |
Preoperative KPS score (higher KPS score) | 0.975 (0.958 to 0.993) | 0.005 | 0.987 (0.965 to 1.009) | 0.231 |
Postoperative KPS score (higher KPS score) | 0.971 (0.956 to 0.987) | 0.0004 | 0.977 (0.961 to 0.993) | 0.006 |
Un-decreased postoperative KPS score | 0.759 (0.508 to 1.133) | 0.177 | - | - |
IDH status of sGBM (mutation) | 0.572 (0.385 to 0.851) | 0.006 | 0.701 (0.465 to 1.055) | 0.088 |
※ KPS = Karnofsky Performance Status |
In addition, multivariate Cox regression analysis revealed that GTR (HR, 0.613; 95% CI, 0.408–0.923; p = 0.019), diagnosis without newly occurring symptoms on follow-up (HR, 0.481; 95% CI, 0.308–0.750; p = 0.001), and high postoperative KPS score (HR, 0.977; 95% CI, 0.961–0.993; p = 0.006) were independent favorable prognostic factors for prolonged OS (Table 2).
Subgroup analysis for prognostic factors for OS
To investigate the factors that affected the OS of patients with various newly occurring symptoms, we divided all recruited patients into four sub-groups based on their new symptoms upon diagnosis with sGBM (Tables 3–6).
Table 3
Univariate and multivariate analysis of secondary OS in sGBM patients in group-R
| Univariate analysis | Multivariate analysis |
HR (95.0% CI) | p value | HR (95.0% CI) | p value |
Age | 0.981 (0.935 to 1.030) | 0.448 | - | - |
Extent of resection (gross total resection) | 0.238 (0.100 to 0.570) | 0.001 | 0.238 (0.100 to 0.570) | 0.001 |
Preoperative KPS score (higher KPS score) | 0.969 (0.937 to 1.003) | 0.071 | - | - |
Postoperative KPS score (higher KPS score) | 1.009 (0.967 to 1.053) | 0.682 | - | - |
Un-decreased postoperative KPS score | 1.472 (0.582 to 3.724) | 0.415 | - | - |
IDH status of sGBM (mutation) | 1.453 (0.634 to 3.331) | 0.377 | - | - |
※ KPS = Karnofsky Performance Status, group-R = patients without any newly occurring symptoms when they were diagnosed as sGBM basing on T1 contrast enhancement MRI when they regularly re-examined. |
Table 4
Univariate and multivariate analysis of secondary OS in sGBM patients in group-E
| Univariate analysis | Multivariate analysis |
HR (95.0% CI) | p value | HR (95.0% CI) | p value |
Age | 0.980 (0.918 to 1.046) | 0.541 | - | - |
Extent of resection (gross total resection) | 0.875 (0.283 to 2.707) | 0.816 | - | - |
Preoperative KPS score (higher KPS score) | 1.013 (0.955 to 1.076) | 0.664 | - | - |
Postoperative KPS score (higher KPS score) | 0.964 (0.928 to 1.001) | 0.056 | - | - |
Un-decreased postoperative KPS score | 0.295 (0.092 to 0.950) | 0.041 | 0.295 (0.092 to 0.950) | 0.041 |
IDH status of sGBM (mutation) | 0.391 (0.122 to 1.252) | 0.114 | - | - |
※ KPS = Karnofsky Performance Status, group-E = patients with newly epilepsy when they were diagnosed as sGBM. |
Table 5
Univariate and multivariate analysis of secondary OS in sGBM patients in group-F
| Univariate analysis | Multivariate analysis |
HR (95.0% CI) | p value | HR (95.0% CI) | p value |
Age | 0.999 (0.960 to 1.041) | 0.974 | - | - |
Extent of resection (gross total resection) | 0.410 (0.204 to 0.822) | 0.012 | 0.410 (0.205 to 0.821) | 0.012 |
Preoperative KPS score (higher KPS score) | 1.005 (0.941 to 1.074) | 0.874 | - | - |
Postoperative KPS score (higher KPS score) | 0.952 (0.924 to 0.982) | 0.002 | 0.988 (0.935 to 1.044) | 0.222 |
Un-decreased postoperative KPS score | 0.400 (0.201 to 0.795) | 0.009 | 0.401 (0.202 to 0.795) | 0.009 |
IDH status of sGBM (mutation) | 0.944 (0.487 to 1.831) | 0.865 | - | - |
※ KPS = Karnofsky Performance Status, group-F = patients with newly functional impairments such as paralysis, aphasia, cognitive functional deficits when they were diagnosed as sGBM. |
Table 6
Univariate and multivariate analysis of secondary OS in sGBM patients in group-O
| Univariate analysis | Multivariate analysis |
HR (95.0% CI) | p value | HR (95.0% CI) | p value |
Age | 0.967 (0.929 to 1.007) | 0.102 | - | - |
Extent of resection (gross total resection) | 0.984 (0.464 to 2.083) | 0.965 | - | - |
Preoperative KPS score (higher KPS score) | 0.984 (0.938 to 1.033) | 0.518 | - | - |
Postoperative KPS score (higher KPS score) | 0.993 (0.965 to 1.021) | 0.603 | - | - |
Un-decreased postoperative KPS score | 0.943 (0.419 to 2.122) | 0.887 | - | - |
IDH status of sGBM (mutation) | 1.049 (0.492 to 2.240) | 0.901 | - | - |
※ KPS = Karnofsky Performance Status, group-O = patients with newly other symptoms, such as headache and/or vomiting, when they were diagnosed as sGBM. |
Using univariate Cox regression analysis, we found that GTR was the only favorable prognostic factor for patients in group R (HR, 0.238; 95% CI, 0.100–0.570; p = 0.001). Moreover, a consistent or increased postoperative KPS score was the only favorable prognostic factor for patients in group E (HR, 0.295; 95% CI, 0.092–0.950; p = 0.041). In addition, for patients in group F, GTR (HR, 0.410; 95% CI, 0.204–0.822; p = 0.012), high postoperative KPS score (HR, 0.952; 95% CI, 0.924–0.982; p = 0.002), and a consistent or increased postoperative KPS score (HR, 0.400; 95% CI, 0.201–0.795; p = 0.009) were favorable prognostic factors. After multivariate Cox regression analysis, GTR (HR, 0.410; 95% CI, 0.204–0.822; p = 0.012) and a consistent or increased postoperative KPS score (HR, 0.401; 95% CI, 0.202–0.795; p = 0.009) were favorable independent factors for patients in group F. Furthermore, no clinical characteristics were found to affect the OS of patients in group O.
OS outcomes for patients with various newly occurring symptoms
After using the Kaplan–Meier method, our results showed that the independent factors GTR and diagnosis without newly occurring symptoms on follow-up could discriminate the OS of patients with sGBM (Fig. 2, the Kaplan–Meier results of other factors are shown in supplemental Fig. 1). We further subdivided the patients into four sub-groups based on their various newly occurring symptoms upon diagnosis with sGBM. Using Kaplan–Meier analysis, the different OS in these four sub-groups were shown. The OS of patients in group E was significantly longer than that of patients in groups F and O (Fig. 3). Groups R, F, and O had similar results. However, there was no significant difference in OS between groups E and R. Additionally, there was no significant difference in OS between groups F and O.