title: Carbon ion radiotherapy decreases the impact of tumor heterogeneity on radiation response in experimental prostate tumors.
abstract: To quantitatively study the impact of intrinsic tumor characteristics and microenvironmental factors on local tumor control after irradiation with carbon ((12)C-) ions and photons in an experimental prostate tumor model.
  
  
  
  Three sublines of a syngeneic rat prostate tumor (R3327) differing in grading (highly (-H) moderately (-HI) or anaplastic (-AT1)) were irradiated with increasing single doses of either (12)C-ions or 6 MV photons in Copenhagen rats. Primary endpoint was local tumor control within 300 days. The relative biological effectiveness (RBE) of (12)C-ions was calculated from the dose at 50% tumor control probability (TCD50) of photons and (12)C-ions and was correlated with histological, physiological and genetic tumor parameters.
  
  
  
  Experimental findings demonstrated that (i) TCD50-values between the three tumor sublines differed less for (12)C-ions (23.6-32.9 Gy) than for photons (38.2-75.7 Gy), (ii) the slope of the dose-response curve for each tumor line was steeper for (12)C-ions than for photons, and (iii) the RBE increased with tumor grading from 1.62 ± 0.11 (H) to 2.08 ± 0.13 (HI) to 2.30 ± 0.08 (AT1).
  
  
  
  The response to (12)C-ions is less dependent on resistance factors as well as on heterogeneity between and within tumor sublines as compared to photons. A clear correlation between decreasing differentiation status and increasing RBE was found. (12)C-ions may therefore be a therapeutic option especially in patients with undifferentiated prostate tumors, expressing high resistance against photons.
authors.affiliation: Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany; Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany. Electronic address: c.glowa@dkfz.de.
authors.forename: Christin
authors.initials: C
authors.lastname: Glowa
authors.affiliation: Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany.
authors.forename: Christian P
authors.initials: CP
authors.lastname: Karger
authors.affiliation: National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany; Heidelberg Ion Beam Therapy Center (HIT), Heidelberg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Brons
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Dawen
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
authors.forename: Ralph P
authors.initials: RP
authors.lastname: Mason
authors.affiliation: Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany; National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany; Department of Molecular Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Huber
authors.affiliation: Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany; National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Debus
authors.affiliation: National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg, Germany; Department of Molecular Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Peschke
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000532:radiotherapy*; D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D063193:Heavy Ion Radiotherapy; D008297:Male; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology / Q000532:radiotherapy*; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D017785:Photons; D011829:Radiation Dosage; D011836:Radiation Tolerance; D051381:Rats; D059016:Tumor Microenvironment
keywords: Carbon ion radiotherapy; Prostate tumor; Relative biological effectiveness (RBE); Tumor heterogeneity