Purpose: Although the association between proton linear energy transfer (LET) and biologic effectiveness is well established in vitro, this association is unclear in patients. Analyzing this association in clinical data is further complicated by confounding factors such as treatment delivery variations. We previously assessed the effect of proton modulation techniques on dose-weighted LET (LET(D)), but the contribution of different acceleration methods to LET(D) variability remained unknown. Therefore, the purpose of this study was to determine the extent to which proton acceleration methods affect LET(D).
Methods: We used TOPAS Monte Carlo transport code to model the protons exiting medical cyclotrons and synchrotrons. We calculated the dose and LET(D) from a single proton beam incident on a virtual water phantom with three treatment delivery conditions: passively scattered (PS) protons from a cyclotron, pencil-beam–scanned (PBS) protons from a cyclotron, and PBS protons from a synchrotron. Treatment plans for all conditions matched the absorbed dose distributions.
Results: Comparing the spatial LET(D) distributions revealed no significant difference between cyclotron- and synchrotron-based treatments with the same modulation technique in (IQR: [2.70, 4.20] keV/μm and [2.65, 4.12] keV/μm, respectively) or near (IQR: [11.89, 14.91] keV/μm and [11.55, 13.94] keV/μm, respectively) the treatment volume. LET(D) significantly differed between the modulation techniques but was unaffected by the acceleration method (average LET(D) ratio (PBS/PS): cyclotron 2.29 +/- 0.44; synchrotron 2.18 +/- 0.39). Furthermore, the spectral fluence incident on the water phantom was characterized by the modulation technique, with minimal variation with acceleration method.
Conclusion: LET(D) is unaffected by different proton acceleration methods but is affected by modulation technique. These results suggest that multicenter studies aiming to elucidate the biologic effectiveness of proton therapy in patients can safely integrate data from synchrotron- and cyclotron-based systems but should exercise caution when considering data from different modulation techniques.