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Boron Neutron Capture Therapy of Brain Tumors: Clinical Trials at the Finnish Facility Using Boronophenylalanine
Authors:Heikki Joensuu  Leena Kankaanranta  Tiina Seppälä  Iiro Auterinen  Merja Kallio  Martti Kulvik  Juha Laakso  Jyrki Vähätalo  Mika Kortesniemi  Petri Kotiluoto  Tom Serén  Johanna Karila  Antti Brander  Eija Järviluoma  Päivi Ryynänen  Anders Paetau  Inkeri Ruokonen  Heikki Minn  Mikko Tenhunen  Juha Jääskeläinen  Markus Färkkilä  Sauli Savolainen
Affiliation:(1) Department of Oncology, University of Helsinki; VTT Processes, VTT, Finland;(2) Department of Physical Sciences, University of Helsinki; VTT Processes, VTT, Finland;(3) VTT Processes, VTT, University of Helsinki, Helsinki, Finland;(4) Department of Neurology, and Clinical Research Institute, University of Helsinki, Helsinki, Finland;(5) Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland;(6) Laboratory of Radiochemistry, University of Helsinki, Helsinki, Finland;(7) Department of Laboratory Diagnostics and Radiology, Helsinki University Central Hospital, Finland;(8) Department of Physical Sciences, Helsinki and Clinical Research Institute and, Finland;(9) VTT Processes, VTT, Helsinki, Finland;(10) Department of Radiology, University of Helsinki, Helsinki, Finland;(11) Department of Pharmacy, University of Helsinki, Helsinki, Finland;(12) Department of Pathology, Helsinki University Central Hospital, Helsinki, Finland;(13) Turku PET Centre, Turku, Helsinki University Central Hospital, Helsinki, Finland;(14) Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland
Abstract:Two clinical trials are currently running at the Finnish dedicated boron neutron capture therapy (BNCT) facility. Between May 1999 and December 2001, 18 patients with supratentorial glioblastoma were treated with boronophenylalanine (BPA)-based BNCT within a context of a prospective clinical trial (protocol P-01). All patients underwent prior surgery, but none had received conventional radiotherapy or cancer chemotherapy before BNCT. BPA-fructose was given as 2-h infusion at BPA-dosages ranging from 290 to 400thinspmg/kg prior to neutron beam irradiation, which was given as a single fraction from two fields. The average planning target volume dose ranged from 30 to 61thinspGy (W), and the average normal brain dose from 3 to 6thinspGy (W). The treatment was generally well tolerated, and none of the patients have died during the first months following BNCT. The estimated 1-year overall survival is 61%. In another trial (protocol P-03), three patients with recurring or progressing glioblastoma following surgery and conventional cranial radiotherapy to 50–60thinspGy, were treated with BPA-based BNCT using the BPA dosage of 290thinspmg/kg. The average planning target dose in these patients was 25–29thinspGy (W), and the average whole brain dose 2–3thinspGy (W). All three patients tolerated brain reirradiation with BNCT, and none died during the first three months following BNCT. We conclude that BPA-based BNCT has been relatively well tolerated both in previously irradiated and unirradiated glioblastoma patients. Efficacy comparisons with conventional photon radiation are difficult due to patient selection and confounding factors such as other treatments given, but the results support continuation of clinical research on BPA-based BNCT.
Keywords:boron neutron capture therapy  BNCT  glioblastoma  glioma  neutron beam radiotherapy  radiotherapy
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