| Autor: |
Thorgersen EB; Department of Gastroenterological Surgery, Oslo University Hospital, The Radium Hospital, Oslo, Norway., Asvall J; Department of Research and Development, Division of Emergencies and Critical Care, Oslo University Hospital, Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Schjalm C; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway., McAdam KE; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway., Bruland ØS; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Oncology, Oslo University Hospital, The Radium Hospital, Oslo, Norway., Larsen SG; Department of Gastroenterological Surgery, Oslo University Hospital, The Radium Hospital, Oslo, Norway., Mollnes TE; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Immunology, Oslo University Hospital Rikshospitalet, Oslo, Norway.; Research Laboratory, Nordland Hospital, Bodø, Norway. |
| Abstrakt: |
Despite extensive treatment with surgery and chemotherapy many patients with peritoneal metastases from colorectal cancer experience intraperitoneal disease relapse. The α-emitting 224 radium-labelled microparticle radionuclide therapeutic Radspherin® is being explored as a novel treatment option for these patients. Radspherin® is specially designed to give local radiation to the surface of the peritoneal cavity and potentially kill remaining attached micrometastases as well as free-floating cancer cells, thus preventing future relapse. The effect of Radspherin® on the immune system is not known. Systemic and local inflammatory responses were analyzed in plasma, intraperitoneal fluid and urine collected prospectively as part of a phase 1 dose-escalation study of intraperitoneal instillation of the α-emitting therapeutic radiopharmaceutical Radspherin®, at baseline and the first 7 postoperative days from nine patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. All patients additionally received intraperitoneal instillation of Radspherin® on postoperative day 2. Complement activation products C3bc and the terminal complement complex were analyzed using enzyme-linked immunosorbent assay. Cytokines ( n = 27), including interleukins, chemokines, interferons and growth factors, were analyzed using multiplex technique. The time course and magnitude of the postoperative cytokine response after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy displayed a modest systemic response in plasma, in contrast to a substantial local intraperitoneal response. After administration of Radspherin®, a significant increase ( P < 0.05) in TNF and MIP-1β was observed in both plasma and peritoneal fluid, whereas IL-9 increased only in plasma and IFNγ and IL1-RA only in peritoneal fluid. Only minor changes were seen for the majority of the inflammatory markers after Radspherin® administration. Our study showed a predominately local rather than systemic inflammatory response to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Radspherin® had overall modest impact on the inflammation. |
