Roadmap: proton therapy physics and biology

Abstract

The treatment of cancer with proton radiation therapy was first suggested in 1946 followed by the first treatments in the 1950s. As of 2020, almost 200 000 patients have been treated with proton beams worldwide and the number of operating proton therapy (PT) facilities will soon reach one hundred. PT has long moved from research institutions into hospital-based facilities that are increasingly being utilized with workflows similar to conventional radiation therapy. While PT has become mainstream and has established itself as a treatment option for many cancers, it is still an area of active research for various reasons: the advanced dose shaping capabilities of PT cause susceptibility to uncertainties, the high degrees of freedom in dose delivery offer room for further improvements, the limited experience and understanding of optimizing pencil beam scanning, and the biological effect difference compared to photon radiation. In addition to these challenges and opportunities currently being investigated, there is an economic aspect because PT treatments are, on average, still more expensive compared to conventional photon based treatment options. This roadmap highlights the current state and future direction in PT categorized into four different themes, 'improving efficiency', 'improving planning and delivery', 'improving imaging', and 'improving patient selection'.

Costs of Definitive Chemoradiation, Surgery, and Adjuvant Radiation Versus De-Escalated Adjuvant Radiation per MC1273 in HPV+ Cancer of the Oropharynx

“…This deviation is qualitatively and quantitatively consistent with an in silico study of Wohlfahrt et al [31], which is relatively comparing the DirectSPR and standard HLUT approach on the level of dose calculation without knowing the ground truth. Our results underline and justify the validity of the magnitude of safety margins used for standard HLUT conversion, especially when also considering the notable inter-center variability in CT-based SPR prediction as recently quantified in a European inter-center comparison [15,32,33] An alternative for in-human range validation is the so-called range probing [34], which is in the phase of translation into clinical application [35]. However, the probing beam is penetrating the full patient to allow for a measurement of the remaining proton range behind the patient.…”

“…Recently, improvements have been made and clinical prototype systems have emerged [38,39]. However, its potential benefit over dual-energy CT has yet to be demonstrated in clinical application [5,15,40].…”

“…While not yet in broad and routine clinical use, the research on prompt gamma imaging (PGI) is driven by its relevance for online-adaptive PT [15]. The applicability of PGI for clinical range verification has already been shown in proof-of-principle experiments in the past, at first for double-scattering (DS) [16] and later pencil-beam-scanning (PBS) treatments in phantoms [17] and patients [18,19].…”

Does the uncertainty in relative biological effectiveness affect patient treatment in proton therapy?

“…1). Whether the increase of the RBE towards the distal edge is a clinical issue, or the use of a fixed RBE of 1.1 is an adequate clinical solution is under debate, and there is an increasing awareness of clinical uncertainties in proton therapy arising from RBE issues [2,[7][8][9].…”

Clinical Implementation of Proton Therapy Using Pencil-Beam Scanning Delivery Combined With Static Apertures

“…The clinical impact of the dose reduction of OARs by several GyRBE, which could be achieved by the insertion of apertures, was difficult to predict. Thus, future studies should seek to improve the NTCP-models, considering both the proton beam radiation quality ( 29 , 30 ) and the irradiation of pediatric patients ( 31 ).…”