title: Irradiation Does Not Increase the Penetration Depth of Doxorubicin in Normal Tissue After Pressurized Intra-peritoneal Aerosol Chemotherapy (PIPAC) in an Ex Vivo Model.
abstract: OBJECTIVE
  To compare the impact of single fractional with bi-fractional irradiation on the depth of doxorubicin penetration into the normal tissue after pressurized intra-peritoneal aerosol chemotherapy (PIPAC) in our ex vivo model.
  
  
  METHODS
  Fresh post mortem swine peritoneum was cut into 12 proportional sections. Two control samples were treated with PIPAC only (no irradiation), one sample on day 1, the other on day 2. Five samples were irradiated with 1, 2, 4, 7 or 14 Gy followed by PIPAC. Four samples were treated on day one with 0.5, 1, 2, 3.5 or 7 Gy and with the same radiation dose 24 h later followed by PIPAC. Doxorubicin was aerosolized in an ex vivo PIPAC model at 12 mmHg/36°C. In-tissue doxorubicin penetration was measured using fluorescence microscopy on frozen thin sections.
  
  
  RESULTS
  Doxorubicin penetration (DP) after PIPAC for the control samples was 407 μm and 373 μm, respectively. DP for samples with single fraction irradiation was 396 μm after 1 Gy, 384 μm after 2 Gy, 327 μm after 4 Gy, 280 μm after 7 Gy and 243 μm after 14 Gy. DP for samples with 2 fractions of irradiation was 376 μm after 0.5+0.5 Gy, 363 μm after 1+1 Gy, 372 μm after 2+2 Gy, 341 μm after 3.5+3.5 and 301 μm after 7+7 Gy irradiation. Fractionating of the irradiation did not significantly change DP into normal tissue.
  
  
  CONCLUSIONS
  Irradiation does not increase the penetration depth of doxorubicin into the normal tissue but might have a limiting impact on penetration and distribution of doxorubicin. Further studies are warranted to investigate the impact of addition of irradiation to PIPAC of tumor cells and to find out if irradiation can be used safely as chemopotenting agent for patients with peritoneal metastases treated with PIPAC.
authors: Department of General Surgery and Therapy Center for Peritonealcarcinomatosis, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany Basic Research Laboratory, Department of Surgery, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany.
authors: Veria
authors: V
authors: Khosrawipour
authors: Department of Nuclear Medicine, University Clinic Essen, Essen, Germany.
authors: Alexander
authors: A
authors: Bellendorf
authors: Basic Research Laboratory, Department of Surgery, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany.
authors: Carolina
authors: C
authors: Khosrawipour
authors: Department of Radiation Oncology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany.
authors: Yousef
authors: Y
authors: Hedayat-Pour
authors: Department of Hematology and Medical Oncology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany.
authors: David
authors: D
authors: Diaz-Carballo
authors: Department of Neuroanatomy and Molecular Brain Research, Ruhr University Bochum, Herne, Germany.
authors: Eckart
authors: E
authors: Förster
authors: Department of Radiation Oncology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany.
authors: Ralph
authors: R
authors: Mücke
authors: Basic Research Laboratory, Department of Surgery, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany.
authors: Burak
authors: B
authors: Kabakci
authors: Department of Radiation Oncology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany.
authors: Irenäus Anton
authors: IA
authors: Adamietz
authors: Basic Research Laboratory, Department of Surgery, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany Department of Radiation Oncology, Marien Hospital Herne, Ruhr University Bochum, Herne, Germany khfmed@yahoo.com.
authors: Khashayar
authors: K
authors: Fakhrian
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage*; D006801:Humans; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy / Q000556:secondary; D010537:Peritoneum / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D011827:Radiation; D013552:Swine
chemical_list: D004317:Doxorubicin
keywords: Ex vivo; drug penetration; peritoneal carcinomatosis; pressurized intra-peritoneal aerosol chemotherapy (PIPAC); radiotherapy