title: Isolated lung perfusion with gemcitabine combined with radiotherapy: no additional lung toxicity in an experimental model.
abstract: OBJECTIVE
  Isolated lung perfusion with gemcitabine is an effective technique for the treatment of lung metastases in an experimental model. In clinical studies, increased toxicity has been observed when combining intravenous gemcitabine with radiotherapy (RT). The goal of our study was to determine whether RT in combination with isolated lung perfusion increases lung toxicity.
  
  
  METHODS
  Rodents were randomized into eight groups: sham group, RT, intravenous gemcitabine, intravenous gemcitabine combined with RT, isolated lung perfusion with hydroxyethyl starch (HES) or gemcitabine, isolated lung perfusion with HES or gemcitabine combined with RT. Gemcitabine was administered in a dose of 40 mg/kg and RT as a single fraction of 8 Gy. The effect on lung tissue was evaluated by % fibrosis in a haematoxylin-eosin stain and by % alveoli that contained siderophages on Perls stain. A total of 36 slices were made per treatment and per stain. The results of different groups were compared using logistic regression.
  
  
  RESULTS
  There were no significant differences between treatment with intravenous gemcitabine and RT. Isolated lung perfusion with gemcitabine showed significant more histopathologic changes compared with intravenous gemcitabine (P < 0.0001). When RT was added, there was no fibrosis after intravenous gemcitabine and mild-to-moderate haemosiderosis. After isolated lung perfusion with gemcitabine combined with RT, there was moderate to severe fibrosis and mild to severe haemosiderosis. Adding RT to isolated lung perfusion with gemcitabine showed no significant difference compared to isolated lung perfusion alone.
  
  
  CONCLUSIONS
  Combination of isolated lung perfusion and RT is feasible in an experimental model. No additional toxicity of RT was observed compared to isolated lung perfusion alone. Further studies are necessary to determine efficacy of this combined treatment.
authors.affiliation: Department of Thoracic and Vascular Surgery, Radiotherapy and Pathology,  Antwerp University Hospital, Edegem,  Belgium.
authors.forename: Jana
authors.initials: J
authors.lastname: Van Thielen
authors.forename: Anouk
authors.initials: A
authors.lastname: Wittock
authors.forename: Jeroen
authors.initials: J
authors.lastname: Hendriks
authors.forename: Willem
authors.initials: W
authors.lastname: den Hengst
authors.forename: Christel
authors.initials: C
authors.lastname: De Pooter
authors.forename: Danielle
authors.initials: D
authors.lastname: Van den Weyngaert
authors.forename: Patrick
authors.initials: P
authors.lastname: Pauwels
authors.forename: Paul
authors.initials: P
authors.lastname: Van Schil
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000633:toxicity*; D059248:Chemoradiotherapy / Q000009:adverse effects*; D010478:Chemotherapy, Cancer, Regional Perfusion / Q000009:adverse effects*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D004334:Drug Administration Schedule; D006486:Hemosiderosis / Q000209:etiology; D007262:Infusions, Intravenous; D016015:Logistic Models; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D008297:Male; D023421:Models, Animal; D011658:Pulmonary Fibrosis / Q000209:etiology; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine