Understanding Relative Biological Effectiveness and Clinical Outcome of Prostate Cancer Therapy Using Particle Irradiation: Analysis of Tumor Control Probability With the Modified Microdosimetric Kinetic Model

Abstract

Purpose: Recent experimental studies and clinical trial results might indicate that - at least for some indications - continued use of the mechanistic model for relative biological effectiveness (RBE) applied at carbon ion therapy facilities in Europe for several decades (LEM-I) may be unwarranted. We present a novel clinical framework for prostate cancer treatment planning and tumor control probability (TCP) prediction based on the modified microdosimetric kinetic model (mMKM) for particle therapy. Methods: Treatment plans of 91 prostate tumor patients (proton: 46, carbon ions: 45) applying 66GyRBE [RBE=1.1 for protons and LEM-I, (α/β)x=2.0Gy, for carbon ions] in 20 fractions were recalculated using mMKM ((α/β)x=3.1Gy). Based solely on the response data of photon-irradiated patient groups stratified according to risk and usage of ADT, we derived parameters for an mMKM-based Poisson-TCP model. Subsequently, new carbon and helium ion plans, adhering to prescribed biological dose criteria, were generated. These were systematically compared to the clinical experience of Japanese centers employing an analogous fractionation scheme and existing proton plans. Results: mMKM predictions suggested significant biological dose deviation between proton and carbon ion arms. Patients irradiated with protons received 3.25±0.08GyRBEmMKM/Fx, while patients treated with carbon ions received 2.51±0.05GyRBEmMKM/Fx. TCP predictions were 86±3% for protons and 52±4% for carbon ions, matching the clinical outcome of 85% and 50%. Newly optimized carbon ion plans, guided by the mMKM/TCP model, effectively replicated clinical data from Japanese centers. Using mMKM, helium ions exhibited similar target coverage as proton and carbon ions and an improved rectum and bladder sparing compared to proton. Conclusions: Our mMKM-based model for prostate cancer treatment planning and TCP prediction was validated against clinical data for proton and carbon ion therapy and its application was extended to helium ion therapy. Based on the data presented in this work, mMKM seems to be a good candidate for clinical biological calculations in carbon ion therapy for prostate cancer.