title: Phase I/II trial evaluating carbon ion radiotherapy for the treatment of recurrent rectal cancer: the PANDORA-01 trial.
abstract: BACKGROUND
  Treatment standard for patients with rectal cancer depends on the initial staging and includes surgical resection, radiotherapy as well as chemotherapy. For stage II and III tumors, radiochemotherapy should be performed in addition to surgery, preferentially as preoperative radiochemotherapy or as short-course hypofractionated radiation. Advances in surgical approaches, especially the establishment of the total mesorectal excision (TME) in combination with sophisticated radiation and chemotherapy have reduced local recurrence rates to only few percent. However, due to the high incidence of rectal cancer, still a high absolute number of patients present with recurrent rectal carcinomas, and effective treatment is therefore needed.Carbon ions offer physical and biological advantages. 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 increase relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the cell line as well as the endpoint analyzed.Japanese data on the treatment of patients with recurrent rectal cancer previously not treated with radiation therapy have shown local control rates of carbon ion treatment superior to those of surgery. Therefore, this treatment concept should also be evaluated for recurrences after radiotherapy, when dose application using conventional photons is limited. Moreover, these patients are likely to benefit from the enhanced biological efficacy of carbon ions.
  
  
  METHODS
  In the current Phase I/II-PANDORA-01-Study the recommended dose of carbon ion radiotherapy for recurrent rectal cancer will be determined in the Phase I part, and feasibilty and progression-free survival will be assessed in the Phase II part of the study.Within the Phase I part, increasing doses from 12 × 3 Gy E to 18 × 3 Gy E will be applied.The primary endpoint in the Phase I part is toxicity, the primary endpoint in the Phase II part is progression-free survival.
  
  
  CONCLUSIONS
  With conventional photon irradiation treatment of recurrent rectal cancer is limited, and the clinical effect is only moderate. With carbon ions, an improved outcome can be expected due to the physical and biological characteristics of the carbon ion beam. However, the optimal dose applicable in this clincial situation as re-irradiation still has to be determined. This, as well as efficacy, is to be evaluated in the present Phase I/II trial.
  
  
  BACKGROUND
  NCT01528683.
authors.affiliation: Deparment of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany. Stephanie.Combs@med.uni-heidelberg.de
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Combs
authors.forename: Meinhard
authors.initials: M
authors.lastname: Kieser
authors.forename: Daniel
authors.initials: D
authors.lastname: Habermehl
authors.forename: Jürgen
authors.initials: J
authors.lastname: Weitz
authors.forename: Dirk
authors.initials: D
authors.lastname: Jäger
authors.forename: Piero
authors.initials: P
authors.lastname: Fossati
authors.forename: Roberto
authors.initials: R
authors.lastname: Orrechia
authors.forename: Rita
authors.initials: R
authors.lastname: Engenhart-Cabillic
authors.forename: Richard
authors.initials: R
authors.lastname: Pötter
authors.forename: Manjit
authors.initials: M
authors.lastname: Dosanjh
authors.forename: Oliver
authors.initials: O
authors.lastname: Jäkel
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Jürgen
authors.initials: J
authors.lastname: Debus
mesh_terms: D000328:Adult; D002244:Carbon / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D012004:Rectal Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D012062:Relative Biological Effectiveness
chemical_list: D002244:Carbon