Prognostic assessment in patients operated for brain metastasis from systemic tumors.

BACKGROUND: Established models for prognostic assessment in patients with brain metastasis do not stratify for prior surgery. Here we tested the prognostic accuracy of the Graded Prognostic Assessment (GPA) score model in patients operated for BM and explored further prognostic factors. METHODS: We included 285 patients operated for brain metastasis at the University Hospital Zurich in the analysis. Information on patient characteristics, imaging, staging, peri- and postoperative complications and survival were extracted from the files and integrated into a multivariate Cox hazard model. RESULTS: The GPA score showed an association with outcome. We further identified residual tumor after surgery (p = 0.007, hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.1-2.3) steroid use (p = 0.021, HR 1.7, 95% CI 1.1-2.6) and number of extracranial metastasis sites (p = 0.009, HR 1.4, 95% CI 1.1-1.6) at the time of surgery as independent prognostic factors. A trend was observed for postoperative infection of the subarachnoid space (p = 0.102, HR 3.5, 95% CI 0.8-15.7). CONCLUSIONS: We confirm the prognostic capacity of the GPA score in a cohort of operated patients with brain metastasis. However, extent of resection and steroid use provide additional aid for the prognostic assessment in these patients.

Postoperative progression of brain metastasis is associated with seizures.

Seizures in patients with brain metastases have an impact on morbidity and quality of life. The influence of tumor growth on the risk of seizures in these patients is not well defined. In this cohort study, we evaluated adult patients from the University Hospital of Zurich following resection of brain metastases from solid tumors, with or without preoperative seizures, at 3, 6, 9, and 12 months postoperatively. Brain magnetic resonance imaging was assessed for tumor progression using the Response Assessment in Neuro-Oncology criteria. The quarterly risk of unprovoked seizures was modeled with mixed effects logistic regression. We analyzed 444 time frames in 220 patients. Progression of brain metastases was independently associated with seizures during the respective quarterly follow-up period (odds ratio = 3.9, 95% confidence interval = 1.3-11.3, p = .014). Complete resection of brain metastases was associated with a lower risk of seizures (odds ratio = .2, 95% confidence interval = .04-.7, p = .015). Postoperative progression of brain metastases quadrupled the risk of seizures; therefore, vigorous follow-up may be useful to identify tumor progression and gauge the risk of seizures. The identification of patients at high seizure risk may have implications for treatment decisions and influence aspects of daily life. Breakthrough seizures may indicate brain metastases progression.

Venous thromboembolic events in patients with brain metastases: the PICOS score.

AIM OF STUDY: Venous thromboembolic events (VTEs) are significant complications in patients with systemic malignancies. Thrombosis risk is poorly defined for patients with brain metastasis, and available risk calculation scores are not validated for these patients. METHODS: We identified 811 patients with brain metastasis followed at our institution and reviewed electronic charts retrospectively for the occurrence of VTEs, along with candidate risk factors. Risk factors were tested in univariate and multivariate analyses and finally integrated in a score model for risk estimation. An independent cohort of 346 patients with brain metastasis was available for validation. RESULTS: VTEs were documented in 97 of 811 patients (12.0%). Primary tumours with high thrombogenicity (p = 0.02, hazard ratio 1.7, 95% confidence interval (CI) = 1.1-2.8), dexamethasone (p = 0.011, hazard ratio 2.27, 95% CI = 1.5-4.5), chemotherapy (p = 0.005, hazard ratio 3.4, 95% CI = 1.6-7.5), body mass index > 35 kg/m2 (p = 0.002, hazard ratio 3.4, 95% CI = 1.6-7.5) and immobilisation (p = 0.003, hazard ratio 2.4, 95% CI = 1.3-4.3) were confirmed to be independently associated with VTEs. We derived a score model for VTE risk estimation, the thrombogenic primary, immobilization, chemotherapy, obesity, steroid (PICOS) score (0-7 points). Receiver-operating characteristic curve analysis demonstrated its prognostic accuracy (area under the curve [AUC] = 0.71, 95% CI = 0.64-0.77), and its value for the evaluation of VTE risk was superior to that of other scores such as the Khorana (AUC = 0.51) or CONKO (AUC = 0.52) scores. The potential value of the PICOS score was confirmed in the validation cohort (AUC = 0.72, 95% CI = 0.63-0.82). CONCLUSIONS: The PICOS score may become a helpful tool for the identification of patients with brain metastasis at high risk for VTEs and for stratification in controlled studies.

Risk factors for the development of epilepsy in patients with brain metastases.

BACKGROUND: Current guidelines do not recommend primary prophylactic anti-epileptic drug (AED) therapy for patients with brain metastases (BM). Yet, subgroups of patients at high seizure risk might still benefit from prophylaxis. METHODS: We identified 799 patients diagnosed with BM by retrospective screening of our electronic chart system. Candidate risk factors for the development of epilepsy were tested by univariate and multivariate Cox regression models. RESULTS: Epilepsy was diagnosed in 226 of 799 patients (28%). Risk factors for epilepsy in non-operated patients were single BM (P = 0.002, hazard ratio [HR] 3.2, 95% CI: 1.5-6.6) and detection of tumoral hemorrhage (P = 0.008, HR 2.5, 95% CI: 1.3-4.9). Preoperative seizures occurred predominantly in patients with supratentorial BM (P = 0.003, HR 20.78, 95% CI: 2.8-153.4) and lung cancer (P = 0.022; HR 2.0, 95% CI: 1.1-3.6). Postoperative seizures were associated with supratentorial localization (P = 0.017, HR 5.8, 95% CI: 1.4-24.3), incomplete resection (P = 0.005, HR 4.6, 95% CI: 1.6-13.1), and by trend for multiple brain surgeries (P = 0.095, HR 1.9, 95% CI: 0.9-4.0). These risk factors were integrated into a predictive score model for postoperative epilepsy (score sum 0-8). A gradual increase of seizure rates along with higher sum score was confirmed post hoc (score 0 = no seizures; score 8 = 48% seizures). Receiver operating characteristic analysis supported diagnostic accuracy (P = 0.00001, area under the curve = 0.75). CONCLUSIONS: Here we have defined risk profiles for the development of BM-related epilepsy and derived a score which might help to estimate the risk of postoperative seizures and identify individuals at risk who might benefit from primary prophylactic AED therapy.

Underweight and weight loss are predictors of poor outcome in patients with brain metastasis.

PURPOSE: Overweight may be associated with favorable outcome whereas tumor cachexia may be associated with worse outcome in patients with metastatic cancer. Here we evaluate the association of abnormal body mass index and weight change with outcome in patients with brain metastasis. METHODS: Patients with a diagnosis of brain metastasis treated at the University Hospital Zurich (n = 703) were assessed for associations of body mass index, weight change, comorbidities and survival. RESULTS: Compared with patients with normal body mass index of 18.5-24.9 kg/m2 and a median overall survival of 9 months (95% confidence interval 7.5-10.5), overall survival was inferior in patients with body mass index < 18.5 kg/m2 (overall survival 6 months, 95% confidence interval 1.6-10.3, p = 0.04), but superior in patients with body mass index > 25 kg/m2 (overall survival 13 months, 95% confidence interval 11.0-15.0; p = 0.033). We report a median relative weight loss of 5% within the first 6 months of diagnosis of brain metastasis (95% confidence interval 3.3-6.5), and reduction exceeding the median was associated with an unfavorable outcome (weight loss < 5% 22.0 months, 95% confidence interval 19.2-24.8; weight loss > 5% 14.0 months, 95% confidence interval 11.9-16.). CONCLUSION: High body mass index is associated with better, and underweight with worse outcome in patients with brain metastasis. Conversely, weight loss above median may predict poor outcome. Future studies need to address whether vigorous treatment of tumor cachexia, e.g. by specific nutrition management, might improve outcome of patients with brain metastasis. In contrast, regimens associated with weight loss such as ketogenic diet may be detrimental.