Proton therapy – Present and future

Abstract

In principle, proton therapy offers a substantial clinical advantage over the conventional photon therapy. This is because of the unique depth-dose characteristics of protons, which can be exploited to achieve significant reductions in normal tissue doses proximal and distal to the target volume. These may, in turn, allow escalation of tumor doses, greater sparing of normal tissues, thus potentially improving local control and survival while at the same time reducing toxicity and improving quality of life. Protons, accelerated to therapeutic energies ranging from 70 to 250 MeV, typically with a cyclotron or a synchrotron, are transported to the treatment room where they enter the treatment head mounted on a rotating gantry. The initial thin beams of protons are spread laterally and longitudinally and shaped appropriately to deliver treatments. Spreading and shaping can be achieved by electro-mechanical means to treat the patients with “passively-scattered proton therapy (PSPT); or using magnetic scanning of thin “beamlets” of protons of a sequence of initial energies. The latter technique can be used to treat patients with optimized intensity modulated proton therapy (IMPT), the most powerful proton modality. Despite the high potential of proton therapy, the clinical evidence supporting the broad use of protons is mixed. It is generally acknowledged that proton therapy is safe, effective and recommended for many types of pediatric cancers, ocular melanomas, chordomas and chondrosarcomas. Although promising results have been and continue to be reported for many other types of cancers, they are based on small studies. Considering the high cost or establishing and operating proton therapy centers, questions have been raised about their cost effectiveness. General consensus is that there is a need to conduct randomized trials and/or collect outcomes data in multi-institutional registries to unequivocally demonstrate the advantage of protons. Treatment planning and plan evaluation of PSPT and IMPT requires special considerations compared to the processes used for photon treatment planning. The differences in techniques arise from the unique physical properties of protons but are also necessary because of the greater vulnerability of protons to uncertainties, especially from inter- and intra-fractional variations in anatomy. These factors must be considered in designing as well as evaluating treatment plans. In addition to anatomy variations, other sources of uncertainty in dose delivered to the patient include the approximations and assumptions of models used for computing dose distributions for planning of treatments. Furthermore, the relative biological effectiveness (RBE) of protons is simplistically assumed to have a constant value of 1.1. In reality, the RBE is variable and a complex function of energy of protons, dose per fraction, tissue and cell type, end point, etc. These uncertainties, approximations and current technological limitations of proton therapy may limit the achievement of the true potential of p...

Hydrogel Spacer Reduces Rectal Dose during Proton Therapy for Prostate Cancer: A Dosimetric Analysis

“…IMPT can reduce the rectal dose relative to PSPT in the absence of spacers [10], as we observed for V60 and V70 in this study. These reductions may be attributed to more precise dose deposition achieved with IMPT, which allows avoidance of normal structures with complex, curved geometries such as the seminal vesicles; IMPT also uses a ''layer-by-layer'' approach to deliver radiation to a target volume [23]. In the present study, including the seminal vesicles in the CTV contributed to the rectal doses being higher in the PSPT-without-spacer plans.…”

Trends and Disparities of Proton Therapy Use among Patients with Head and Neck Cancer: Analysis from the National Cancer Database (2005-14)

“…There is also uncertainty in the physical properties of protons for changes in density and volumes that could affect dose delivery [12]. Lateral scatter is also a concern, although the integral dose is lower [2]. Taken together, it is worth considering the possibility of reporting bias with toxicity rates tracked more carefully for newer technologies.…”

“…A study by van der Laan et al [1] found that patients treated with intensity-modulated proton therapy had decreased dose to the pharyngeal constrictors, resulting in decreased rates of dysphagia compared with IMRT. Furthermore, several comparison studies [2][3][4][5] have shown lower energy delivered to regions outside the target and, thus, lower integral dose with proton therapy.…”

Potential skin morbidity reduction with intensity-modulated proton therapy for breast cancer with nodal involvement

“…This is not a novelty and it has been discussed and demonstrated in silico since the first studies in the early 2000s [28][29][30]. However, the actual clinical use of PT for the treatment of the whole breast is gaining momentum thanks to the recent gradual spread of proton therapy centers and to the increasing use of PBS techniques and optimized IMPT [31][32][33]. There are at least eight clinical trials currently investigating the use of proton therapy for the treatment of the whole breast with or without nodal irradiation [34].…”