Brain metastases as first presentation of malignancy: Immediate management, differential diagnosis; prevalence of primaries and suggested work-up Symposium on Brain Metastasis Cancer Center Zurich Zurich, January 19, 2018 Michael Weller Department of Neurology & Brain Tumor Center University Hospital Zurich Frauenklinikstrasse 26 CH-8091 Zurich michael.weller@usz.ch
Brain (and leptomeningeal) metastasis: clinical presentation and differential diagnosis Incidentaloma Seizures Stroke Side effect of drug therapy Paraneoplastic syndrome Comorbidity Cognitive decline Typical signs of leptomeningeal metastases
Brain metastases from cancer of unknown primary site (BM-CUPS) 25% of cancer patients may develop brain metastases (BM), associated with unfavorable outcome 30% of BM patients exhibit neurological symptoms as first manifestation of systemic malignancy (BM-CUPS) Detection of primary tumor and assessment of extracranial metastases are crucial for therapy planning and probably outcome Gavrilovic & Posner. J Neurooncol 2005;75:5-14, Barnholtz-Sloan et al. Neuro Oncol 2012;14:910-8
Diagnostic work-up of BM-CUPS patients Most BM-CUPS stem from lung cancer, melanoma and renal cell cancer Chest (abdomen) CT traditionally diagnostic gold standard in BM-CUPS patients Agazzi et al. Acta Neurochir (Wien) 2004;146:153-7, Mavrakis et al. Neurology 2005;65:908-11 18 F-fluordesoxyglucose positron emission tomography (FDG- PET)/CT data for primary detection and staging in BM-CUPS patients limited Klee et al. Eur J Neurol 2002;9:657-62 Staging by FDG-PET/CT versus CT chest/abdomen may reduce futile diagnostic procedures in patients with systemic cancer Reinhardt et al. J Clin Oncol 2006;24:1178-87, Fischer et al. N Engl J Med 2009;361:32-9
Figure 1 Consort chart BM-CUPS cohort of the University Hospital Zurich Alternative Diagnosis N=292 Incomplete chart N=44 Only extracranial metastases N=82 Search-term BM positive N=985 Confirmed diagnosis of BM N=565 Diagnosis of BM before detection of primary (CUPS) N=126 Diagnosis of BM after detection of primary (non-cups) N=439 CT only N=31 PET only N=18 CT and PET N=77 CT thorax only N=13 Sensitivity to spot primary lesion Staging capabilities N=64
BM-CUPS cohort Zurich Patients characteristics Figure 2 A Histology Gastrointestinal Mamma Gynecological other Hematological Hepatobiliar Lung (NSCLC) Lung (SCLC) Lung (not conclusive) Melanoma Prostatic Renal cell Sarcoma Testicular Thyroid Urogenital Pancreatic Not conclusive CUPS non-cups 0 50 100 150 200 250 Patients [number] B Age (median (range)) 61.1 (38-85) Gender (number F/M) 31/33 Number of metastases (median (range)) 1.0 (1-7) Days to detect primary (median (range)) 3.0 (0-50) C Primary not identified Renal cell 4.0 % carcinoma 4.0 % Melanoma 7.9 % Lung (not conclusive) 2.4 % Colorectal cancer 1.6 % Lung (SCLC) 12.7 % Lung (NSCLC) 65.9 %
Patient characteristics in the validation cohort Lille & Vienna Figure A.2 (online only): Characteristics of BM-CUPS patients in the validation cohort A Median Age (range) 58.0 (25-87) Gender (number, F/M) 35/90 Median number of metastases (range) 1 (1-10) Days until detection of primary (median) 8 (0-371) C Diagnosis of BM before detection of primary (CUPS) N=220 B Histology not Renal cell carcinoma conclusive 1% 1% Melanoma 5% other 1% Colorectal cancer 10% CT only N=93 PET only N=0 CT and PET N=127 CT thorax only N=2 Lung 82% Sensitivity to spot primary lesion Staging capabilities N=125
Detection of the primary tumor Zurich versus Lille / Vienna
Staging properties of CT versus PET-CT Zurich cohort Figure A.1 (online only): Staging pathway. No further lesion N=36 Patients with FDG-PET/CT and chest/abdomen CT N=64 Further lesion by FDG-PET/CT N=28 Extracranial lesion assessed by biopsy N=18 No biopsy, significance unclear N=10 Further tumor lesion - metastasis N=9 - other tumor N=1 Pathologic lymph node N=4 Benign lesion N=4 Not covered by chest/ abdomen CT N=4 Not covered by chest/abdomen CT N=2
CONCLUSIONS Diagnostic work-up of BM-CUPS patients FDG-PET does not detect (statistically) more primary tumors than chest/abdomen CT FDG-PET detects more extracranial metastases and thereby induces GPA migration FDG-PET is more expensive, may trigger expensive further work-up and may trigger procedures with risk: does this benefit/risk/ratio justify its use and how could this be explored in a clinical trial?