title: 5-ALA-induced fluorescence behavior of reactive tissue changes following glioblastoma treatment with radiation and chemotherapy.
abstract: BACKGROUND
  The 5-aminolevulinic acid (5-ALA) fluorescence-guided resection of recurrent malignant glioma is a standard surgical procedure at many neuro-oncological centers and is considered to be equally reliable as the primary resection of these tumors. 5-ALA induced fluorescence (5-AIF)-guided resection has been demonstrated to be highly predictive for tumor tissue. As pseudoprogression and radiation-induced necrosis are critical differential diagnoses of glioma recurrence, the purpose of the present analysis was to analyze 5-AIF behavior in resected tissue specimens histopathologically showing regressive and reactive changes but lacking active, that is, cellular recurrent tumor tissue after adjuvant treatment of malignant glioma.
  
  
  METHODS
  A retrospective analysis was performed in patients suffering from malignant glioma who underwent surgical resection for suspected contrast-enhancing tumor recurrence (according to RANO criteria) at our institution between 2007 and 2013, but in whom histopathological analysis only revealed reactive changes. The presence of AIF in the resected tissue samples was intraoperatively assessed and classified by the surgeon, using the categories (1) no, (2) vague and (3) solid AIF.
  
  
  RESULTS
  A total of 13 out of 313 patients who underwent AIF-guided surgical resection of tissue suspicious for recurrent glioma histologically demonstrated only reactive changes without active recurrent tumor tissue after adjuvant therapy. Pretreatment was chemotherapy with temozolomide in 1 patient and combined radio-/chemotherapy in 12 patients. Six patients had suffered previous tumor recurrence with a subsequently intensified adjuvant therapy. Seven of the 13 patients displayed solid, 5 patients vague and 1 patient no 5-AIF of the resected tissue specimens. However, all 5-AIF-positive lesions exhibited heterogeneous fluorescence patterns with vaguely or solidly fluorescent as well as nonfluorescent regions.
  
  
  CONCLUSIONS
  Resection of reactive tissue without active recurrent tumor after multimodal treatment for glioblastoma is frequently associated with solid or vague 5-AIF. Therefore, neurosurgeons should remain cautious when attempting to employ intraoperative 5-AIF to discriminate radiation- and chemotherapy-induced tissue changes from true disease progression. Nevertheless, 5-AIF-guided resection remains a valid tool in the neurosurgical treatment of recurrent gliomas.
authors.affiliation: Department of Neurosurgery, Medical Faculty, Heinrich Heine University Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Germany, marcelalexander.kamp@med.uni-duesseldorf.de.
authors.forename: Marcel A
authors.initials: MA
authors.lastname: Kamp
authors.forename: Jörg
authors.initials: J
authors.lastname: Felsberg
authors.forename: Hosai
authors.initials: H
authors.lastname: Sadat
authors.forename: Jamshid
authors.initials: J
authors.lastname: Kuzibaev
authors.forename: Hans-Jakob
authors.initials: HJ
authors.lastname: Steiger
authors.forename: Marion
authors.initials: M
authors.lastname: Rapp
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
authors.forename: Maxiné
authors.initials: M
authors.lastname: Dibué
authors.forename: Michael
authors.initials: M
authors.lastname: Sabel
mesh_terms: D000368:Aged; D000622:Aminolevulinic Acid; D001932:Brain Neoplasms / Q000175:diagnosis / Q000601:surgery*; D018450:Disease Progression; D005260:Female; D005453:Fluorescence; D005909:Glioblastoma / Q000175:diagnosis / Q000601:surgery*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000601:surgery*; D019635:Neurosurgical Procedures / Q000592:standards*; D017319:Photosensitizing Agents; D012189:Retrospective Studies
chemical_list: D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid