title: Brain Metastasis in Colorectal Cancer Patients: Survival and Analysis of Prognostic Factors.
abstract: BACKGROUND
  The purpose of the study was to characterize the rare cohort of patients (pts) with metastatic colorectal cancer (mCRC) and brain metastasis (BM) and to identify prognostic subgroups.
  
  
  METHODS
  In collaboration with the Munich Cancer Registry, pts with mCRC and BM who were diagnosed between 1998 and 2011 were identified. Survival from the time of first diagnosis of colorectal cancer (CRC) (OS-1), from the time of diagnosis of metastatic disease (OS-2) and of BM (OS-3) was calculated regarding (1) the temporal occurrence of extra- and intracranial metastasis (meta- vs. synchronous) and (2) tumor and patient characteristics. For survival analysis the Kaplan-Meier estimator and Cox regression models were used.
  
  
  RESULTS
  A total of 228 pts (134 male [59%], 94 female [41%]) were identified. The median age was 63 years (142 pts [62%] were 65 years of age or younger). Most pts presented with primary tumors staged T3/4, N+, Grade 2. The primary tumor was located predominantly in the left colon (155 pts; 68%), especially in the rectum (95 pts; 42%). Median OS-1 was 35.6 months (95% confidence interval [CI], 30.1-41.1 months), OS-2 was 16.5 months (95% CI, 13.9-19.1 months), and OS-3 was 2.0 months (95% CI, 1.5-2.5 months). Median time from first CRC diagnosis to BM was 29.2 months. Subsequent BM after extracranial metastasis were observed in 184 pts (80.7%), whereas 31 pts (13.6%) presented with solitary BM. Univariate analysis did not reveal a prognostic variable for overall survival after diagnosis of BM.
  
  
  CONCLUSIONS
  This study presents the largest number of pts with mCRC and BM analyzed to date. The results show that most mCRC pts develop BM as a late step in the course of disease. Median time from first CRC diagnosis to BM is 29.2 months. Only a few pts were diagnosed with BM early in the disease or with solitary BM. When BM is present survival is poor.
authors.affiliation: Department of Hematology and Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center Munich (CCCM), Ludwig-Maximilians-University of Munich, Munich, Germany. Electronic address: Marlies.Michl@med.uni-muenchen.de.
authors.forename: Marlies
authors.initials: M
authors.lastname: Michl
authors.affiliation: Department of Hematology and Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center Munich (CCCM), Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Thurmaier
authors.affiliation: Munich Cancer Registry (MCR), IBE / Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schubert-Fritschle
authors.affiliation: Munich Cancer Registry (MCR), IBE / Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Max
authors.initials: M
authors.lastname: Wiedemann
authors.affiliation: Institute of Medical Informatics, Biometry and Epidemiology (IBE), Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Rüdiger P
authors.initials: RP
authors.lastname: Laubender
authors.affiliation: Department of Surgery, Klinikum Neuperlach, Städtisches Klinikum München, Munich, Germany.
authors.forename: Natascha C
authors.initials: NC
authors.lastname: Nüssler
authors.affiliation: Department of Surgery, Klinikum Neuperlach, Städtisches Klinikum München, Munich, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ruppert
authors.affiliation: Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kleeff
authors.affiliation: Department of Gastroenterology, Hepatology and Gastrointestinal Oncology, Klinikum Bogenhausen, Städtisches Klinikum München, Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schepp
authors.affiliation: Department of Surgery, Krankenhaus Barmherzige Brüder München, Munich, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Reuter
authors.affiliation: Department of Surgery, Klinikum Landshut, Landshut, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Löhe
authors.affiliation: Department of Hematology, Oncology and Palliative Care, Städtisches Klinikum Harlaching und Neuperlach, Munich, Germany.
authors.forename: Meinolf
authors.initials: M
authors.lastname: Karthaus
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Neumann
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirchner
authors.affiliation: Munich Cancer Registry (MCR), IBE / Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany; Institute of Medical Informatics, Biometry and Epidemiology (IBE), Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Engel
authors.affiliation: Department of Hematology and Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center Munich (CCCM), Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000175:diagnosis / Q000473:pathology* / Q000556:secondary; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000473:pathology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D012042:Registries; D016019:Survival Analysis; D015996:Survival Rate; D013997:Time Factors
keywords: Brain metastasis; CNS metastasis; Metastatic colorectal cancer; Subgroups; Survival