title: Interstitial photodynamic therapy of nonresectable malignant glioma recurrences using 5-aminolevulinic acid induced protoporphyrin IX.
abstract: OBJECTIVE
  Limited knowledge of the light and temperature distribution within the target volume in combination with non-selective accumulation of the applied photosensitizers (PS) has hampered the clinical relevance of interstitial photodynamic therapy (iPDT) for treatment of malignant glioma patients. The current pilot study focused on the development and the clinical implementation of an accurate and reproducible irradiation scheme for iPDT using 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PPIX) as a selectively working PS.
  
  
  METHODS
  Monte Carlo simulations of fluence rate and heat transport simulations were performed using the optical properties of normal brain tissue infiltrated by tumor cells (absorption coefficient micro(a) = 0.2 cm(-1), reduced scattering coefficient: micro'(s) = 20 cm(-1)). A modified 3-D treatment-planning software was used to calculate both, the treatment-volume and the exact position of the light diffusers within the lesion. The feasibility and the risk of iPDT were tested in 10 patients with small and circumscribed recurrent malignant gliomas.
  
  
  RESULTS
  The optimum distance between the implanted light diffusers was determined to be 9 mm with regard to both fluence rate and temperature distribution. For this distance a temperature increase above 42 degrees C was not expected to occur. Up to six cylindrical light diffusers were stereotactically implanted to achieve a complete irradiation of the tumor volume, which was possible in every single patient (mean tumor volume: 5.9 cm3). The total applied light fluence was between 4,320 J and 11,520 J. Side effects of iPDT were not observed. Median survival was 15 months.
  
  
  CONCLUSIONS
  5-ALA iPDT in combination with a 3-D treatment-planning (which was based on optical and thermal simulations) is a safe and feasible treatment modality. The clinical impact of these findings deserves further prospective evaluation.
authors.affiliation: Laser Research Laboratory, Ludwig-Maximilians-University, Marchioninistr. 23, 81377 Munich, Germany. tbeck@med.uni-muenchen.de
authors.forename: Tobias J
authors.initials: TJ
authors.lastname: Beck
authors.forename: Friedrich W
authors.initials: FW
authors.lastname: Kreth
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Beyer
authors.forename: Jan H
authors.initials: JH
authors.lastname: Mehrkens
authors.forename: Andreas
authors.initials: A
authors.lastname: Obermeier
authors.forename: Herbert
authors.initials: H
authors.lastname: Stepp
authors.forename: Walter
authors.initials: W
authors.lastname: Stummer
authors.forename: Reinhold
authors.initials: R
authors.lastname: Baumgartner
mesh_terms: D000328:Adult; D000368:Aged; D000622:Aminolevulinic Acid / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D005240:Feasibility Studies; D005910:Glioma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009010:Monte Carlo Method; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D010865:Pilot Projects; D011524:Protoporphyrins / Q000378:metabolism*; D016634:Radiosurgery
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX