Rectum Dose Constraints for Carbon Ion Therapy: Relative Biological Effectiveness Model Dependence in Relation to Clinical Outcomes

Kyungdon Choi; Silvia Molinelli; Stefania Russo; Alfredo Mirandola; Maria Rosaria Fiore; Barbara Vischioni; Piero Fossati; Rachele Petrucci; Irene Turturici; Jon Espen Dale; Francesca Valvo; Mario Ciocca; Andrea Mairani

doi:10.3390/cancers12010046

Rectum Dose Constraints for Carbon Ion Therapy: Relative Biological Effectiveness Model Dependence in Relation to Clinical Outcomes

Cancers (Basel). 2019 Dec 21;12(1):46. doi: 10.3390/cancers12010046.

Authors

Affiliations

¹ Clinical Department, Centro Nazionale di Adroterapia Oncologica, 27100, Pavia, Italy.
² Department of Physics, University of Pavia, 27100 Pavia, Italy.
³ Medical Department, MedAustron Ion Therapy Center, 2700 Wiener Neustadt, Austria.
⁴ Department of Diagnostic Imaging, Molecular Imaging, Interventional Radiology and Radiotherapy, University of Roma Policlinico TorVergata, 00133 Roma, Italy.
⁵ Department of Oncology and Medical Physics, Haukeland University Hospital, 1400 Bergen, Norway.
⁶ BioPT Group, Heidelberg Ion-Beam Therapy Center, 69120 Heidelberg, Germany.

Abstract

The clinical application of different relative biological effectiveness (RBE) models for carbon ion RBE-weighted dose calculation hinders a global consensus in defining normal tissue constraints. This work aims to update the local effect model (LEM)-based constraints for the rectum using microdosimetric kinetic model (mMKM)-defined values, relying on RBE translation and the analysis of long-term clinical outcomes. LEM-optimized plans of treated patients, having suffered from prostate adenocarcinoma (n = 22) and sacral chordoma (n = 41), were recalculated with the mMKM using an in-house developed tool. The relation between rectum dose-volume points in the two RBE systems (D_LEM|v and D_MKM|v) was fitted to translate new LEM-based constraints. Normal tissue complication probability (NTCP) values, predicting late rectal toxicity, were obtained by applying published parameters. No late rectal toxicity events were reported within the patient cohort. The rectal toxicity outcome was confirmed using dosimetric analysis: D_MKMVHs lay largely below original constraints; the translated D_LEM|v values were 4.5%, 8.3%, 18.5%, and 35.4% higher than the nominal D_MKM|v of the rectum volume, v-1%, 5%, 10% and 20%. The average NTCP value ranged from 5% for the prostate adenocarcinoma, to 0% for the sacral chordoma group. The redefined constraints, to be confirmed prospectively with clinical data, are D_LEM|5cc ≤ 61 Gy(RBE) and D_LEM|1cc ≤ 66 Gy(RBE).

Keywords: FRoG; RBE modeling; carbon ion therapy; rectum constraints.