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).
Highlights
The physical and radiobiological characteristics of carbon ion beams, i.e., finite range, inverse depth dose profile, sharp lateral penumbra and increased relative biological effectiveness (RBE) at the end of range, make them suitable and potentially advantageous for the treatment of tumors thatCancers 2020, 12, 46; doi:10.3390/cancers12010046 www.mdpi.com/journal/cancersCancers 2020, 12, 46 are radio-resistant to conventional radiotherapy and/or in close proximity to critical organs at risk (OARs) [1]
Japanese centers use either the semi-phenomenological mixed-beam model [8], or the modified microdosimetric kinetic model [9]. These latter two models have been clinically validated at the NIRS for their consistency and both will be referred to here as mMKM [10]
The best model fitting the relation between local effect model (LEM) and mMKM Dv was a quadratic regression: DMKM|v = a × (DLEM|v )2 + b × DLEM|v + c, (1)
Summary
The physical and radiobiological characteristics of carbon ion beams, i.e., finite range, inverse depth dose profile, sharp lateral penumbra and increased relative biological effectiveness (RBE) at the end of range, make them suitable and potentially advantageous for the treatment of tumors thatCancers 2020, 12, 46; doi:10.3390/cancers12010046 www.mdpi.com/journal/cancersCancers 2020, 12, 46 are radio-resistant to conventional radiotherapy and/or in close proximity to critical organs at risk (OARs) [1]. Comparing clinical results obtained with carbon ion radiotherapy (CIRT) at different institutions is, not always straightforward—as the reported nominal RBE-weighted doses depend critically on the different RBE models used [2,3,4]. Japanese centers use either the semi-phenomenological mixed-beam model [8], or the modified microdosimetric kinetic model (mMKM) [9]. These latter two models have been clinically validated at the NIRS for their consistency and both will be referred to here as mMKM [10]. Several studies concerning rectum tolerance doses and normal tissue complication probability (NTCP)
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