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

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 (DLEM|v and DMKM|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: DMKMVHs lay largely below original constraints; the translated DLEM|v values were 4.5%, 8.3%, 18.5%, and 35.4% higher than the nominal DMKM|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 DLEM|5cc ≤ 61 Gy(RBE) and DLEM|1cc ≤ 66 Gy(RBE).

Conversion and Validation of Rectal Constraints for Prostate Carcinoma Receiving Hypofractionated Carbon-ion Radiotherapy With a Local Effect Model

“…NIRS published their rectum dose constraints for 16-fraction CIRT [10 , 14] with MKM, which were percentage volume constraints. Choi [15] et al from Centro Nazionale di Adroterapia Oncologica (CNAO), Italy, rst converted NIRS constraints to LEM. Based on that, they additionally injected their experience and published their own constraints, which were absolute volume constraints.…”

Conversion and validation of rectal constraints for prostate carcinoma receiving hypofractionated carbon-ion radiotherapy with a local effect model

“…Our previous study converted the MKM experience to LEM [ 12 ] and successfully applied the converted constraints to our dose-escalation clinical trial, which examined dose escalations to 4.10 Gy (RBE) per fraction by 16 fractions. The Centro Nazionale di Adroterapia Oncologica (CNAO) converted the NIRS experience to LEM and summarized their own experiences, eventually finalizing their own rectum constraints [ 13 ]. All the aforementioned constraints were for 16-fraction protocol.…”

RBE-weighted dose conversions for patients with recurrent nasopharyngeal carcinoma receiving carbon-ion radiotherapy from the local effect model to the microdosimetric kinetic model

“…Adaptation of the OAR constraints was absolutely necessary. So far, only LEM dose constraints of the optical nerve [ 16 ] and rectum [ 17 , 18 ] have been reformulated; no studies have been carried for recurrent tumors (e.g., rNPC). Since the OARs of patients with rNPC (e.g., optical nerve, spinal cord, and brain stem) have already exposed to a sufficient amount of radiation, stricter OAR constraints should be discussed.…”