title: Use of an artificial lymphatic system during carboplatin infusion to improve canine osteosarcoma blood flow and clinical response.
abstract: BACKGROUND
  The artificial lymphatic system (ALS), a mechanical system designed to reduce increased interstitial fluid pressure in solid tumors and enhance the delivery of chemotherapy, was evaluated within a randomized clinical trial treating spontaneously occurring canine appendicular osteosarcoma (OS), a tumor similar to its human OS counterpart.
  
  
  METHODS
  An ALS was investigated for its ability to increase OS blood flow and increase uptake of intravenously administered carboplatin.
  
  
  RESULTS
  Blood flow increased by 314% in tumors with active ALS drains versus 126% in control tumors (P < .03). Tumor carboplatin uptake increased by 51% after drain activation (P = .07). Microvascular density (MVD) was measured in tumors after surgical amputation and in corresponding bone regions in a cohort of normal dogs. The OS tumors had equivalent MVD as normal bone, and MVD was higher in the humerus than the femur (P < .03) in both tumor and normal bone. Median survival between the ALS-treated and control cohorts was not different despite increased drug uptake or ALS manipulation. Compared with historic controls, ALS drain insertion into tumors to reduce interstitial fluid pressure did not worsen the prognosis.
  
  
  CONCLUSIONS
  The findings in canine spontaneously occurring OS indicate that an ALS may be of value as a chemotherapy adjunct for enhancing the delivery of chemotherapy to tumor interstitium.
authors.affiliation: Orthopaedic Surgical Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York, 10021-6007, USA. direstag@mskcc.org
authors.forename: Gene R
authors.initials: GR
authors.lastname: DiResta
authors.forename: Sean W
authors.initials: SW
authors.lastname: Aiken
authors.forename: Holly K
authors.initials: HK
authors.lastname: Brown
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Bergman
authors.forename: Ann
authors.initials: A
authors.lastname: Hohenhaus
authors.forename: E J
authors.initials: EJ
authors.lastname: Ehrhart
authors.forename: Keith
authors.initials: K
authors.lastname: Baer
authors.forename: John H
authors.initials: JH
authors.lastname: Healey
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001187:Artificial Organs; D001706:Biopsy; D001859:Bone Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000662:veterinary*; D016190:Carboplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015331:Cohort Studies; D004283:Dog Diseases / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D005260:Female; D005269:Femur; D006811:Humerus; D007262:Infusions, Intravenous; D008208:Lymphatic System; D008297:Male; D012516:Osteosarcoma / Q000098:blood supply* / Q000188:drug therapy* / Q000662:veterinary*; D010100:Oxygen / Q000378:metabolism; D012039:Regional Blood Flow; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016190:Carboplatin; D010100:Oxygen