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.

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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/m 2 (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.

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 Lastly, breakthrough seizures may be a sign of BM progression and should trigger prompt follow-up MRI.

BACKGROUND: Despite increased risk of comorbidities, overweight may be associated with improved outcome in patients with metastatic cancer. Conversely, tumor cachexia has been identified as a negative predictor of outcome in patients with brain metastasis (BM) from lung cancer. Here we evaluate the association of abnormal body mass index (BMI) and weight change with outcome in patients with BM from different primary tumors. METHODS: Patients with a diagnosis of BM diagnosed and treated at the University Hospital Zurich (n=703) were assessed for associations of BMI, weight change, comorbidities and survival. RESULTS: Compared with patients with normal BMI of 18.5–24.9 kg/m2 who experienced a median overall survival (OS) of 9 months (95% confidence interval (CI) 7.5–10.5), OS was inferior in patients with BMI< 18.5 kg/m2 (OS 6 months, 95% CI 1.6–10.3, p=0.04), but superior in patients with BMI >25 kg/m2 (OS 13 months, 95% CI 11.0–15.0; p=0.033). For patients with documented weight course (n=173 of 703), we report a median relative weight loss of 5% within the first 6 months of BM diagnosis (95% CI 3.3–6.5). Reduction above the median was associated with an unfavorable outcome in this subgroup (weight loss ≧5% 22.0 months, 95% CI 19.2–24.8; weight loss < 5% 14.0 months, 95% CI 11.9–16.). CONCLUSIONS: Despite being associated with a worse cardiovascular risk profile, high BMI is associated with preferable and underweight with poor outcome in BM patients. Conversely, weight loss above median may be a predictor of poor outcome. Future studies need to address the question whether vigorous treatment of tumor cachexia, e.g. by specific nutrition management, might improve outcome of BM patients. In contrast, regimens that are associated with weight loss such as ketogenic diet may be detrimental.

BACKGROUND Venous thromboembolic events are significant complications in patients and possibly associated with an unfavorable outcome. Thrombosis risk is poorly defined for patients with brain metastasis, and available risk calculation scores are not validated for these patients. MATERIAL AND METHODS We identified 811 patients with brain metastasis followed at our institution and screened electronic charts retrospectively for the occurrence of venous thromboembolic events, along with candidate risk factors. Risk factors were tested in uni- and multivariate analyses and finally integrated in a score model for risk prediction. RESULTS Venous thromboembolic events were documented in 97 of 811 patients (12.0%). Primary tumors with high thrombogenicity (p=0.02, odds ratio 1.7, 95% CI 1.1–2.8), dexamethasone (p=0.011, odds ratio 2.27, 95% CI 1.5–4.5), chemotherapy (p=0.005, odds ratio 3.4, 95% CI 1.6–7.5), BMI > 35 kg/m2 (p=0.002, odds ratio 3.4, 95% CI 1.6–7.5) and immobilization (p=0.003, odds ratio 2.4, 95% CI 1.3–4.3) were confirmed as independent predictors of VTE. We derived a score model for venous thromboembolic event prediction, the PICOS (thrombogenic Primary, Immobilization, Chemotherapy, Obesity, Steroids) score (0–7 points). Receiver Operating Characteristic Curve Analysis demonstrated its prognostic accuracy (AUC=0.71, 95% CI 0.64–0.77), and its predictive capability was superior to that of other scores proposed for the evaluation of venous thromboembolic event risk such as the Khorana (AUC=0.51) or CONKO (AUC=0.52) scores. CONCLUSION We report a rate of venous thrombotic events of 12.0% in our cohort of 811 patients with brain metastasis. We define a risk model for prediction in of venous thrombotic events in patients with BM, the PICOS score. It may become a valuable tool for the identification of brain metastasis patients at high risk for venous thromboembolic events and be helpful for guidance of clinicians towards decision whether to start thrombosis prophylaxis. Further, the PICOS score might be used for stratification in controlled studies.

Brain metastases (BM) from systemic cancer are the most common intracranial tumors. 1,2 Advances in multidisciplinary therapeutic concepts have improved outcome, from a median overall survival (OS) of about 4 months more than 20 years ago 3 to more than 30 months in selected subgroups of contemporary large patient cohorts. 4 Besides radiotherapy, chemotherapy, targeted therapies, and immunotherapy, neurosurgery has been established decades ago as an option for local treatment in patients with symptomatic BM or oligometastasis and a favorable overall condition. [5][6][7][8][9] Improvement of surgical techniques by development of intraoperative MRI and electrophysiological

BACKGROUND: Venous thromboembolic events are significant complications in patients and possibly associated with an unfavorable outcome. 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 screened electronic charts retrospectively for the occurrence of venous thromboembolic events, along with candidate risk factors. Risk factors were tested in uni- and multivariate analyses and finally integrated in a score model for risk prediction. RESULTS: Venous thromboembolic events were documented in 97 of 811 patients (12.0%). Primary tumors with high thrombogenicity (p=0.02, odds ratio 1.7, 95% CI 1.1–2.8), dexamethasone (p=0.011, odds ratio 2.27, 95% CI 1.5–4.5), chemotherapy (p=0.005, odds ratio 3.4, 95% CI 1.6–7.5), BMI > 35 kg/m2 (p=0.002, odds ratio 3.4, 95% CI 1.6–7.5) and immobilization (p=0.003, odds ratio 2.4, 95% CI 1.3–4.3) were confirmed as independent predictors of VTE. We derived a score model for venous thromboembolic event prediction, the PICOS (thrombogenic Primary, Immobilization, Chemotherapy, Obesity, Steroids) score (0–7 points). Receiver Operating Characteristic Curve Analysis demonstrated its prognostic accuracy (AUC=0.71, 95% CI 0.64–0.77), and its predictive capability was superior to that of other scores proposed for the evaluation of venous thromboembolic event risk such as the Khorana (AUC=0.51) or CONKO (AUC=0.52) scores. CONCLUSIONS: We report a rate of venous thrombotic events of 12.0% in our cohort of 811 patients with brain metastasis. We define a risk model for prediction in of venous thrombotic events in patients with BM, the PICOS score. It may become a valuable tool for the identification of brain metastasis patients at high risk for venous thromboembolic events and be helpful for guidance of clinicians towards decision whether to start thrombosis prophylaxis. Further, the PICOS score might be used for stratification in controlled studies.