Prognostic factors for survival of patients with glioblastoma: recursive partitioning analysis

Abstract

Survival for patients with glioblastoma multiforme is short, and current treatments provide limited benefit. Therefore, there is interest in conducting phase 2 trials of experimental treatments in newly diagnosed patients. However, this requires historical data with which to compare the experimental therapies. Knowledge of prognostic markers would also allow stratification into risk groups for phase 3 randomized trials. In this retrospective study of 832 glioblastoma multiforme patients enrolled into prospective clinical trials at the time of initial diagnosis, we evaluated several potential prognostic markers for survival to establish risk groups. Analyses were done using both Cox proportional hazards modeling and recursive partitioning analyses. Initially, patients from 8 clinical trials, 6 of which included adjuvant chemotherapy, were included. Subsequent analyses excluded trials with interstitial brachytherapy, and finally included only nonbrachytherapy trials with planned adjuvant chemotherapy. The initial analysis defined 4 risk groups. The 2 lower risk groups included patients under the age of 40, the lowest risk group being young patients with tumor in the frontal lobe only. An intermediate-risk group included patients with Karnofsky performance status (KPS) >70, subtotal or total resection, and age between 40 and 65. The highest risk group included all patients over 65 and patients between 40 and 65 with either KPS<80 or biopsy only. Subgroup analyses indicated that inclusion of adjuvant chemotherapy provides an increase in survival, although that improvement tends to be minimal for patients over age 65, for patients over age 40 with KPS less than 80, and for those treated with brachytherapy.

Fig. 1

Recursive partitioning analysis for all patients (N = 832). For terminal nodes (□), median survival and the 95% confidence interval for the median are given. N = number of patients. Estimates with an asterisk (*) exclude 40 patients missing KPS and 2 patients missing extent of resection.

Fig. 2

Survival for all patients, by risk group. Fourteen patients in group 1, 12 patients in group 2, and 9 patients in group 3 lived beyond 5 years (260 weeks). Individual survival times (including those for patients who are censored) are indicated by a solid circle (•). Fifty-three patients were censored (13 in group 1, 14 in group 2, 21 in group 3, and 5 in group 4). Additional detail is given in Table 4.

Fig. 3

Recursive partitioning analysis for all patients on non-brachytherapy protocols (n = 660). For terminal nodes (□), median survival and the 95% confidence interval for the median are given. N = number of patients. *Twenty-eight patients without KPS were excluded from the estimates.

Fig. 4

Recursive partitioning analysis for all patients on non-brachytherapy protocols that included adjuvant chemotherapy (n = 437). For terminal nodes (□), median survival and the 95% confidence interval for the median are given. N = number of patients. *Twenty-eight patients with missing KPS were excluded from the estimates.

Fig. 5

Survival for patients on nonbrachytherapy protocols that included adjuvant chemotherapy. Nine patients in group 1, 6 patients in group 2, and 7 patients in group 3 survived beyond 5 years (260 weeks). Individual survival times (including those for patients that are censored) are indicated by a solid circle (•). Forty-four patients were censored (12 in group 1, 8 in group 2, 21 in group 3, and 3 in group 4). Additional detail is given in Table 6.

Fig. 6

Survival for all patients on brachytherapy protocols (n = 160). Risk groups are as defined in Table 4 for all patients. Three patients in group 1 and 5 patients in group 2 lived beyond 5 years (260 weeks). Individual survival times (including those for patients that are censored) are indicated by a solid circle (•). Eight patients were censored (1 in group 1, 5 in group 2, 2 in group 3, and 0 in group 4).

Fig. 7

Survival for patients on brachytherapy protocols that included adjuvant chemotherapy (n = 49). Risk groups are as defined for all patients in Table 4. Two patients in group 1 and 2 patients in group 2 lived beyond 5 years (260 weeks). Individual survival times (including those for patients that are censored) are indicated by a solid circle (•). Two patients were censored (both in group 2).