Prognostication of Brain-Metastasized Patients Receiving Subsequent Systemic Therapy: A Single-Center Long-Term Follow-Up

Abstract

Background: Survival of patients with brain metastases (BMs) is poor. It has become clear that targeted therapy has an effect on BMs and patient' prognosis. The question remains which patients benefit from additional systemic therapy. This assumption was evaluated in a large single-center cohort.

Methods: Patients consecutively planned to undergo local radiotherapy for their BMs in 2006-2017 were selected (n = 200). Prognosis, using CERENAL, disease-specific graded prognostic assessment (DS-GPA), and Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA), was evaluated.

Results: Ninety-three (46.5%) patients received at least one additional line of systemic therapy subsequent to the diagnosis of their BMs. The median overall survival (OS) was 6.3 months. Having received subsequent systemic therapy resulted in a more favorable OS (10.4 versus 3.9 months). Interestingly, using dichotomized scores, CERENAL showed prognostic properties in all patients for disease-specific survival on multivariate analysis, whereas RTOG RPA and DS-GPA were not withheld in the model. Lastly, only having a favorable DS-GPA resulted in prolonged progression-free survival for first systemic therapy following BM diagnosis.

Conclusions: Receiving subsequent systemic therapy has a profound influence on outcome in patients with BMs, indicating the effect of systemic therapy on BMs. Use of the CERENAL brain prognostic score shows potential for further prognostication of patients with more favorable outcomes.

Keywords: brain metastases; prognosis; retrospective analysis; survival outcome; targeted therapy.

Figure 1

OS outcomes for brain metastasis prognostic scores. Y-axis depicts cumulative survival (%), X-axis depicts survival time in months. OS curves are shown for: (A) RTOG RPA in the ITT cohort (p = 0.0001), (B) DS-GPA in the ITT cohort (p = 0.0003), (C) CERENAL in the ITT cohort (p < 0.0001), (D) RTOG RPA in patients who did not receive subsequent systemic therapy (p = 0.0319), (E) DS-GPA in patients who did not receive subsequent systemic therapy (p = 0.0010), (F) CERENAL in patients who did not receive subsequent systemic therapy (p < 0.0001), (G) RTOG RPA in patients who received subsequent systemic therapy (p = 0.0003), (H) DS-GPA in patients who received subsequent systemic therapy (p = 0.0148), and (I) CERENAL in patients who received subsequent systemic therapy (p = 0.0002). HRs (95% CIs) are indicated in each survival graph. CI, confidence interval; DS-GPA, diagnosis-specific graded prognostic assessment; HR, hazard ratio; OS, overall survival; RTOG RPA, Radiation Therapy Oncology Group recursive partitioning analysis.

Figure 2

DSS outcome for brain metastasis prognostic scores. Y-axis depicts cumulative survival (%), X-axis depicts survival time in months. DSS curves are demonstrated for: (A) RTOG RPA in the ITT cohort (p = 0.0005), (B) DS-GPA in the ITT cohort (p = 0.0003), (C) CERENAL in the ITT cohort (p < 0.0001), (D) RTOG RPA in patients who did not receive subsequent systemic therapy (p = 0.0589), (E) DS-GPA in patients who did not receive subsequent systemic therapy (p = 0.0008), (F) CERENAL in patients who did not receive subsequent systemic therapy (p < 0.0001), (G) RTOG RPA in patients who received subsequent systemic therapy (p = 0.0015), (H) DS-GPA in patients who received subsequent systemic therapy (p = 0.0140), and (I) CERENAL in patients who received subsequent systemic therapy (p = 0.0004). HRs (95% CIs) are indicated in each survival graph. CI, confidence interval; DS-GPA, diagnosis-specific graded prognostic assessment; DSS, disease-specific survival; HR, hazard ratio; RTOG RPA, Radiation Therapy Oncology Group recursive partitioning analysis.