Background
Prospective cohort study and scoring system development. 1,852 patients with brain metastases from solid tumors treated with whole brain RT (WBRT) at multiple institutions. Developed and validated a prognostic score (WBRT prognostic score) to predict OS after WBRT, identifying patients most likely to benefit vs those for whom comfort-focused care is preferable. Rades D et al, JCO 2016.
Interventions and follow up
Arm A: WBRT: 20 Gy/5, 30 Gy/10, or 40 Gy/20 fractions per physician discretio
Primary endpoint: OS post-WBRT; performance of new prognostic score
mFollow up: 1.0 year
Primary endpoint: OS post-WBRT; performance of new prognostic score
mFollow up: 1.0 year
Results
Comparison: Prognostic score vs established scores (RTOG-RPA, GPA) for OS prediction
Independent prognostic factors: KPS, extracranial metastases, number of brain metastases, primary tumor type, age
Score performance (C-index): New score outperformed RTOG-RPA (C=0.68 vs 0.61)
mOS (favorable score): 10 months vs poor score 2 months
Independent prognostic factors: KPS, extracranial metastases, number of brain metastases, primary tumor type, age
Score performance (C-index): New score outperformed RTOG-RPA (C=0.68 vs 0.61)
mOS (favorable score): 10 months vs poor score 2 months
Adverse events
Main adverse events: WBRT at all dose/fractionation schedules: alopecia universal, fatigue 30%, cognitive effects with prolonged survival. Grade ≥3 acute toxicity <5%. Dexamethasone-related side effects in majority (hyperglycemia, infection).
Conclusions
A new prognostic score combining KPS, extracranial mets, brain met number, primary tumor type, and age accurately identifies brain metastasis patients with favorable vs poor prognosis after WBRT. This guides treatment decisions — identifying patients for whom WBRT is unlikely to benefit vs those who may benefit from more aggressive management.
Key Limitations
Key Limitations: Retrospective cohort. Treatment was not randomized. WBRT technique and dose varied. Molecular driver status not incorporated. Does not address the question of WBRT vs SRS for limited brain metastases — which is addressed by EORTC 22952 and NCCTG N0574.
Clinical Context
Prognostic scoring (RTOG-RPA, GPA, Rades score) is now standard in clinical decision-making for brain metastases treatment. Patients with poor prognosis (KPS <60, uncontrolled systemic disease, multiple brain metastases) are increasingly offered supportive care or SRS over WBRT. WBRT is reserved for patients with multiple brain metastases, leptomeningeal disease, or radiosensitive histologies.
References