title: The metastatic infiltration at the metastasis/brain parenchyma-interface is very heterogeneous and has a significant impact on survival in a prospective study.
abstract: The current approach to brain metastases resection is macroscopic removal of metastasis until reaching the glial pseudo-capsule (gross total resection (GTR)). However, autopsy studies demonstrated infiltrating metastatic cells into the parenchyma at the metastasis/brain parenchyma (M/BP)-interface.
  
  
  OBJECTIVE
  To analyze the astrocyte reaction and metastatic infiltration pattern at the M/BP-interface with an organotypic brain slice coculture system. Secondly, to evaluate the significance of infiltrating metastatic tumor cells in a prospective biopsy study. Therefore, after GTR, biopsies were obtained from the brain parenchyma beyond the glial pseudo-capsule and analyzed histomorphologically.
  
  
  RESULTS
  The coculture revealed three types of cancer cell infiltration. Interestingly, the astrocyte reaction was significantly different in the coculture with a benign, neuroectodermal-derived cell line. In the prospective biopsy study 58/167 (34.7%) samples revealed infiltrating metastatic cells. Altogether, 25/39 patients (64.1%) had proven to exhibit infiltration in at least one biopsy specimen with significant impact on survival (OS) (3.4 HR; p = 0.009; 2-year OS was 6.6% versus 43.5%). Exceptionally, in the non-infiltrating cohort three patients were long-term survivors.
  
  
  CONCLUSIONS
  Metastatic infiltration has a significant impact on prognosis. Secondly, the astrocyte reaction at the M/BP-interface is heterogeneous and supports our previous concept of the organ-specific defense against metastatic (organ-foreign) cells.
authors: Department of Neurosurgery, University Medical Center, Göttingen, Germany.
authors: Laila
authors: L
authors: Siam
authors: Department of Hematology and Medical Oncology, University Medical Center, Göttingen, Germany.|Department of Medical Statistics, University Medical Center, Göttingen, Germany.
authors: Annalen
authors: A
authors: Bleckmann
authors: Department of Hematology and Medical Oncology, University Medical Center, Göttingen, Germany.
authors: Han-Ning
authors: HN
authors: Chaung
authors: Department of Neuroradiology, University Medical Center, Göttingen, Germany.
authors: Alexander
authors: A
authors: Mohr
authors: Department of Hematology and Medical Oncology, University Medical Center, Göttingen, Germany.
authors: Florian
authors: F
authors: Klemm
authors: Institute of Neuropathology, University Medical Center, Göttingen, Germany.
authors: Alonso
authors: A
authors: Barrantes-Freer
authors: Department of Hematology and Medical Oncology, University Medical Center, Göttingen, Germany.
authors: Raquel
authors: R
authors: Blazquez
authors: Department of Radiotherapy and Radiation Oncology, University Medical Center, Göttingen, Germany.
authors: Hendrik A
authors: HA
authors: Wolff
authors: Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany.
authors: Florian
authors: F
authors: Lüke
authors: Department of Neurosurgery, University Medical Center, Göttingen, Germany.
authors: Veit
authors: V
authors: Rohde
authors: Institute of Neuropathology, University Medical Center, Göttingen, Germany.
authors: Christine
authors: C
authors: Stadelmann
authors: Department of Hematology and Medical Oncology, University Medical Center, Göttingen, Germany.|Department of Internal Medicine III, Hematology and Medical Oncology, University Hospital Regensburg, Regensburg, Germany.
authors: Tobias
authors: T
authors: Pukrop
mesh_terms: D000368:Aged; D001253:Astrocytes / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D001921:Brain / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D001932:Brain Neoplasms / Q000378:metabolism / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000556:secondary*; D002465:Cell Movement; D049109:Cell Proliferation; D018920:Coculture Techniques; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D061986:MCF-7 Cells; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D009457:Neuroglia / Q000473:pathology; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor
keywords: astrocytes; brain metastasis; glial-pseudo capsule; metastatic infiltration; organ-specific defense