scope:

Introduction

According to the World Health Organization, cancer is the leading cause of death worldwide. A large portion of cancer patients (e.g., more than half of all cancer patients in the United States) receive radiation therapy during the course of treatment. Radiation therapy is used either as the sole treatment or, more typically, in combination with other therapies, including surgery and chemotherapy.

Radiation interacts with tissue via atomic and nuclear interactions. The energy transferred to and deposited in the tissue in such interactions is quantified as "absorbed dose" and expressed in energy (Joules) absorbed per unit mass (kg), which has the units of Gray (Gy). Depending on the number and spatial correlation of such interactions, mainly with cellular DNA, they can result in mutations or complete functional disruption (i.e., cell death). Assessing radiation damage is a complex problem because the cell typically does have the limited ability to repair certain types of lesions.

There are many degrees of freedom when administering radiation, for example, different radiation modalities, doses, and beam directions. The main focus in research and development of radiation therapy is on eradicating cancerous tissue while minimizing the irradiation of healthy tissue. The ideal scenario would be to treat the designated target without damaging any healthy structures. This is not possible for various reasons such as uncertainties in defining the target volume as well as delivering the therapeutic dose as planned. Furthermore, applying external beam radiation therapy typically requires the beam to penetrate healthy tissue in order to reach the target.

Treatment planning in radiation therapy uses mathematical and physical formalisms to optimize the trade-off between delivering a high and conformal dose to the target and limiting the doses to critical structures. The dose tolerance levels for critical structures, as well as the required doses for various tumor types, are typically defined on the basis of decades of clinical experience.

When considering the trade-off between administering the prescribed target dose and the dose to healthy tissue, the term "therapeutic ratio" is often used. The therapeutic ratio can be defined as the ratio of the probabilities for tumor eradication and normal tissue complication. Technological advances in beam delivery and treatment modality focus mainly on increasing the therapeutic ratio. Improvements can be achieved, for example, by applying advanced imaging techniques leading to improved patient setup or tumor localization.

A gain in the therapeutic ratio can also be expected when using proton therapy instead of conventional photon or electron therapy. The rationale for using proton beams instead of photon beams is the feasibility of delivering higher doses to the tumor while maintaining the total dose to critical structures or maintaining the target dose while reducing the total dose to critical structures.

The most prominent difference between photon and proton beams is the finite range of a proton beam. After a short build-up region, photon beams show an exponentially decreasing energy deposition with increasing depth in tissue. Except for superficial lesions, a higher dose to the tumor compared with the organ at risk can only be achieved by using multiple beam directions. Furthermore, a homogenous dose distribution can only be achieved by utilizing various different beam angles, not by delivering a single field. In contrast, the energy transferred to tissue by protons is inversely proportional to the proton velocity as protons lose their energy mainly in electromagnetic interactions with orbital electrons of atoms. The more the protons slow down, the higher the energy they transfer to tissue per track length, causing the maximum dose deposition at a certain depth in tissue. For a single proton, the peak is very sharp. For a proton beam, it is broadened into a peak of typically a few millimeters width because of the statistical distribution of the proton tracks. The peak is called the Bragg peak (Figure 1). This feature allows pointing a beam toward a critical structure. The depth and width of the Bragg peak is a function of the beam energy and the material (tissue) heterogeneity in the beam path. The peak depth can be influenced by changing the beam energy and can thus be positioned within the target for each beam direction. Although protons from a single beam direction are able to deliver a homogeneous dose throughout the target (by varying the beam energy), multiple beam angles are also used in proton therapy to even further optimize the dose distribution with respect to organs at risk. Note that there is also a slight difference between photon and proton beams when considering the lateral penumbra. For large depths (more than ~16 cm), the penumbra for proton beams is slightly wider than the one for photon beams by typically a few millimeters. Depending on the site, this can be a slight disadvantage of proton beams.