Results of a prospective randomized trial on long-term effectiveness of protons and carbon ions in prostate cancer: LEM I and α/β = 2 Gy overestimates the RBE

Aim To analyze the long-term effectiveness of carbon ions relative to protons in the prospective randomized controlled ion prostate irradiation (IPI) trial. Methods Effectiveness via PSA assessment in a randomized study on prostate irradiation with 20x3.3 Gy(RBE) protons versus carbon ions was analyzed in 92 patients. Proton RBE was based on a fixed RBE of 1.1 while the local effect model (LEM) I and an α/β = 2 Gy was used for carbon ions. The dose in the prostate was recalculated based on the delivered treatment plan using LEM I and LEM IV and different α/β values. Results Five-year overall and progression free survival was 98% and 85% with protons and 91% and 50% with carbon ions, respectively, with the latter being unexpectedly low compared to Japanese carbon ion data and rather corresponding to a photon dose <72 Gy in 2 Gy fractions. According to LEM I and the applied α/β-value of 2 Gy, the applied carbon ion dose in 2 Gy(RBE) fractions (EQD2) was 87.46 Gy(RBE). Recalculations confirmed a strong dependence of RBE-weighted dose on the α/β ratio as well as on the RBE-model. Conclusion The data demonstrate a significant lower effectiveness of the calculated RBE-weighted dose in the carbon ion as compared to the proton arm. LEM I and an α/β = 2 Gy overestimates the RBE for carbon ions in prostate cancer treatment. Adjusting the biological dose calculation by using LEM I with α/β = 4 Gy could be a pragmatic way to safely escalate dose in carbon ion radiotherapy for prostate cancer.