title: Phase i study evaluating the treatment of patients with hepatocellular carcinoma (HCC) with carbon ion radiotherapy: the PROMETHEUS-01 trial.
abstract: BACKGROUND
  Treatment options for patients with advanced hepatocellular carcinoma (HCC) are often limited. In most cases, they are not amenable to local therapies including surgery or radiofrequency ablation. The multi-kinase inhibitor sorafenib has shown to increase overall survival in this patient group for about 3 months.Radiation therapy is a treatment alternative, however, high local doses are required for long-term local control. However, due to the relatively low radiation tolerance of liver normal tissue, even using stereotactic techniques, delivery of sufficient doses for successful local tumor control has not be achieved to date.Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 2 and 3 depending on the HCC cell line as well as the endpoint analyzed.Japanese Data on the evaluation of carbon ion radiation therapy showed promising results for patients with HCC.
  
  
  METHODS
  In the current Phase I-PROMETHEUS-01-Study, carbon ion radiotherapy will be evaluated for patients with advanced HCC. The study will be performed as a dose-escalation study evaluating the optimal carbon ion dose with respect to toxicity and tumor control.Primary endpoint is toxicity, secondary endpoint is progression-free survival and response.
  
  
  CONCLUSIONS
  The Prometheus-01 trial ist the first trial evaluating carbon ion radiotherapy delivered by intensity-modulated rasterscanning for the treatment of HCC. Within this Phase I dose escalation study, the optimal dose of carbon ion radiotherapy will be determined.
  
  
  BACKGROUND
  NCT 01167374.
authors.affiliation: Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. stephanie.combs@med.uni-heidelberg.de
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Combs
authors.forename: Daniel
authors.initials: D
authors.lastname: Habermehl
authors.forename: Tom
authors.initials: T
authors.lastname: Ganten
authors.forename: Jan
authors.initials: J
authors.lastname: Schmidt
authors.forename: Lutz
authors.initials: L
authors.lastname: Edler
authors.forename: Iris
authors.initials: I
authors.lastname: Burkholder
authors.forename: Oliver
authors.initials: O
authors.lastname: Jäkel
authors.forename: Thomas
authors.initials: T
authors.lastname: Haberer
authors.forename: Jürgen
authors.initials: J
authors.lastname: Debus
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D002244:Carbon / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007477:Ions / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011879:Radiotherapy Dosage; D055815:Young Adult
chemical_list: D007477:Ions; D002244:Carbon