Abstract

Symptomatic brain metastases (BM) are a frequent and late complication in cancer patients. However, a subgroup of cancer patients presents with BM as the first symptom of metastatic cancer. Here we aimed to analyze the clinical course and prognostic factors of this particular BM patient population. Patients presenting with newly diagnosed BM without a history of metastatic cancer were identified from the Vienna Brain Metastasis Registry. Clinical characteristics and overall survival were retrieved by chart review. 459/2419 (19.0%) BM patients presented with BM as first symptom of advanced cancer. In 374/459 (81.5%) patients, an extracranial primary tumor, most commonly lung cancer, could be identified within 3 months after BM diagnosis. In 85/459 (18.5%) patients no extracranial primary tumor could be identified despite comprehensive diagnostic workup within the first 3 months after diagnosis of BM. Survival of patients with identified extracranial tumor differed only numerically from patients with cancer of unknown primary (CUP), however patients receiving targeted therapy after molecular workup showed significantly enhanced survival (20 months vs. 7 months; p = 0.003; log rank test). The GPA score showed a statistically significant association with median overall survival times in the CUP BM patients (class I: 46 months; class II: 7 months; class III: 4 months; class IV: 2 months; p < 0.001; log rank test). The GPA score has a strong prognostic value in patients with CUP BM and may be useful for patient stratification in the clinical setting. Comprehensive diagnostic workup including advanced imaging techniques and molecular tissue analyses appears to benefit patients by directing specific molecular targeted therapies.

Highlights

  • Brain metastases (BM) are a frequent and devastating complication occurring in up to 10–30% of patients with advanced cancer

  • 459/2419 (19.0%) patients treated for newly diagnosed BM between 1990 and 2015 at the Medical University of Vienna presented with BM without any history of extracranial metastatic cancer and were included for further analysis (Fig. 1)

  • Patients with BM as first manifestation of advanced cancer remain a clinical challenge in oncology

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Summary

Introduction

Brain metastases (BM) are a frequent and devastating complication occurring in up to 10–30% of patients with advanced cancer. A fraction of patients has been reported to present with BM as first symptom of cancer [1,2,3]. The clinical management of patients with simultaneous BM and extracranial advanced cancer includes the local therapy to control BM symptoms and comprehensive diagnostic workup to guide further treatment strategies. Limited information on the clinical course, survival outcomes and prognostic factors of CUP BM patients are available, such data would be of interest for the clinical management and planning of clinical trials in this particular patient cohort with high medical need. We aimed to analyze clinical characteristics and prognostic factors in patients presenting with BM as first manifestation of metastatic cancer and in particular the sub-cohort of CUP BM patients

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