Survival prediction model of children with diffuse intrinsic pontine glioma based on clinical and radiological criteria

Abstract

Background: Although diffuse intrinsic pontine glioma (DIPG) carries the worst prognosis of all pediatric brain tumors, studies on prognostic factors in DIPG are sparse. To control for confounding variables in DIPG studies, which generally include relatively small patient numbers, a survival prediction tool is needed.

Methods: A multicenter retrospective cohort study was performed in the Netherlands, the UK, and Germany with central review of clinical data and MRI scans of children with DIPG. Cox proportional hazards with backward regression was used to select prognostic variables (P < .05) to predict the accumulated 12-month risk of death. These predictors were transformed into a practical risk score. The model's performance was validated by bootstrapping techniques.

Results: A total of 316 patients were included. The median overall survival was 10 months. Multivariate Cox analysis yielded 5 prognostic variables of which the coefficients were included in the risk score. Age ≤3 years, longer symptom duration at diagnosis, and use of oral and intravenous chemotherapy were favorable predictors, while ring enhancement on MRI at diagnosis was an unfavorable predictor. With increasing risk score categories, overall survival decreased significantly. The model can distinguish between patients with very short, average, and increased overall survival (medians of 7.0, 9.7, and 13.7 mo, respectively). The area under the receiver operating characteristic curve was 0.68.

Conclusions: We developed a DIPG survival prediction tool that can be used to predict the outcome of patients and for stratification in trials. Validation of the model is needed in a prospective cohort.

Keywords: brainstem neoplasms; glioma; magnetic resonance imaging; pons; prognosis.

Fig. 1.

Two patients with DIPG who underwent T1-weighted MRI with contrast: (a) the tumor shows a small nodular enhancement (arrow), which was therefore not scored as ring enhancement; (b) the tumor shows a large area of ring enhancement (arrow).

Fig. 2.

Kaplan–Meier estimates of the DIPG risk score (RS). Based on the risk score, 3 categories were identified: a standard risk arm (RS <1), an intermediate risk arm (RS 1–6), and a high-risk arm (RS ≥ 7). The increasing risk arms correlated with decreasing OS time (log-rank P < .0001 and generalized Wilcoxon P < .0001).