Fabian Wolpert1, Michael Weller2, Anna Sophie Berghoff3, Elisabeth Rushing4, Lisa Michaela Füreder3, Gregory Petyt5, Henning Leske4, Nicolaus Andratschke6, Luca Regli7, Marian Christoph Neidert7, Roger Stupp8, Rolf Stahel8, Reinhard Dummer9, Thomas Frauenfelder10, Patrick Roth2, Nicolas Reyns11, Philipp Antonio Kaufmann12, Matthias Preusser3, Emilie Le Rhun13. 1. Department of Neurology and Brain Tumor Center, University Hospital and University of Zurich, Frauenklinikstrasse 26, CH-8091, Zurich, Switzerland. Electronic address: fabian.wolpert@usz.ch. 2. Department of Neurology and Brain Tumor Center, University Hospital and University of Zurich, Frauenklinikstrasse 26, CH-8091, Zurich, Switzerland. 3. Department of Medicine I, Clinical Division of Oncology, Comprehensive Cancer Center-CNS Tumours Unit (CCC-CNS), Medical University of Vienna, 18-20 Waehringer Guertel, AT-1090, Vienna, Austria. 4. Department of Neuropathology, University Hospital Zurich, Schmelzbergstrasse 12, CH-8091, Zurich, Switzerland. 5. Department of Nuclear Medicine, Lille University, CHU Lille, 59000, Lille, France. 6. Department of Radiation Oncology, University Hospital Zurich, Rämistrasse 100, CH-8091, Zurich, Switzerland. 7. Department of Neurosurgery, University Hospital Zurich, Frauenklinikstrasse 10, CH-8091, Zurich, Switzerland. 8. Department of Oncology, University Hospital Zurich, Rämistrasse 100, CH-8091, Zurich, Switzerland. 9. Department of Dermatology, University Hospital Zurich, Gloriastrasse 31, CH-8091, Zurich, Switzerland. 10. Institute of Diagnostic and Interventional Radiology, University Hospital Zurich, Rämistrasse 100, CH-8091, Zurich, Switzerland. 11. Department of Neurosurgery, Lille University, Inserm, CHU Lille, U1189 - ONCO THAI - Image Assisted Laser Therapy for Oncology, 59000, Lille, France. 12. Department of Nuclear Medicine, University Hospital Zurich, Rämistrasse 100, CH-8091, Zurich, Switzerland. 13. Department of Neurology and Brain Tumor Center, University Hospital and University of Zurich, Frauenklinikstrasse 26, CH-8091, Zurich, Switzerland; Neuro-oncology, Department of Neurosurgery, University Hospital Lille, Salengro Hospital, Rue Emile Laine, FR-59037, Lille, France; Neurology, Department of Medical Oncology, Oscar Lambret Center, FR-59020, Lille, France; Inserm U-1192, Villeneuve d'Ascq, France.
Abstract
BACKGROUND: In 30% of patients with brain metastasis (BM), neurological symptoms are the first clinical manifestation of systemic malignancy, referred to as BM from cancer of unknown primary site (BM-CUPS). Here, we define the diagnostic value of 18F-fluordesoxyglucose positron emission tomography (FDG-PET/CT) in the workup of BM-CUPS. METHODS: We screened 565 patients operated for BM at the University Hospital Zurich and identified 64 patients with BM-CUPS with data on both FDG-PET/CT and contrast-enhanced chest/abdomen computed tomography (CT) available at BM diagnosis. A cohort of 125 patients with BM-CUPS from Lille and Vienna was used for validation. RESULTS: FDG-PET/CT was not superior to chest/abdomen CT in localising the primary lesion in the discovery cohort, presumably because most primary tumours were lung cancers. However, FDG-PET/CT identified additional lesions suspicious of extracranial metastases in 27 of 64 patients (42%). The inclusion of FDG-PET/CT findings shifted the graded prognostic assessment (GPA) score from 3 with CT alone to 2.5 for PET/CT (p = 3.8 × 10-5, Wilcoxon's test), resulting in a predicted survival of 5.3 versus 3.8 months (p = 6.1 × 10-5; Wilcoxon's test). All observations were confirmed in the validation cohort. CONCLUSIONS: Lung cancers are the most common primary tumour in BM-CUPS; accordingly, CT alone shows similar overall sensitivity for detecting the primary tumour as FDG-PET/CT. Yet, FDG-PET/CT improves the accuracy of staging by detecting more metastases, reflected by decreased GPA scores and decreased predicted survival. Therefore, randomised trials on patients with BM should standardise methods of staging, notably when stratifying for GPA.
BACKGROUND: In 30% of patients with brain metastasis (BM), neurological symptoms are the first clinical manifestation of systemic malignancy, referred to as BM from cancer of unknown primary site (BM-CUPS). Here, we define the diagnostic value of 18F-fluordesoxyglucose positron emission tomography (FDG-PET/CT) in the workup of BM-CUPS. METHODS: We screened 565 patients operated for BM at the University Hospital Zurich and identified 64 patients with BM-CUPS with data on both FDG-PET/CT and contrast-enhanced chest/abdomen computed tomography (CT) available at BM diagnosis. A cohort of 125 patients with BM-CUPS from Lille and Vienna was used for validation. RESULTS: FDG-PET/CT was not superior to chest/abdomen CT in localising the primary lesion in the discovery cohort, presumably because most primary tumours were lung cancers. However, FDG-PET/CT identified additional lesions suspicious of extracranial metastases in 27 of 64 patients (42%). The inclusion of FDG-PET/CT findings shifted the graded prognostic assessment (GPA) score from 3 with CT alone to 2.5 for PET/CT (p = 3.8 × 10-5, Wilcoxon's test), resulting in a predicted survival of 5.3 versus 3.8 months (p = 6.1 × 10-5; Wilcoxon's test). All observations were confirmed in the validation cohort. CONCLUSIONS:Lung cancers are the most common primary tumour in BM-CUPS; accordingly, CT alone shows similar overall sensitivity for detecting the primary tumour as FDG-PET/CT. Yet, FDG-PET/CT improves the accuracy of staging by detecting more metastases, reflected by decreased GPA scores and decreased predicted survival. Therefore, randomised trials on patients with BM should standardise methods of staging, notably when stratifying for GPA.
Authors: L M Füreder; G Widhalm; B Gatterbauer; K Dieckmann; J A Hainfellner; R Bartsch; C C Zielinski; M Preusser; A S Berghoff Journal: Clin Exp Metastasis Date: 2018-11-12 Impact factor: 5.150