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Trikalinos TA, Terasawa T, Ip S, et al. Particle Beam Radiation Therapies for Cancer [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2009 Nov. (Comparative Effectiveness Technical Briefs, No. 1.)

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Particle Beam Radiation Therapies for Cancer [Internet].

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Photon Beam Radiotherapy

Most types of cancer radiotherapy use ionizing photon (X-ray or gamma-ray) beams for the local or regional treatment of disease. Ionizing radiation damages the DNA of tumor and healthy cells alike, triggering complex biochemical reactions and eventually resulting in prolonged abnormal cell function and cellular death. Cellular damage increases with (absorbed) radiation dose (measured in Gray units, Gy) – the amount of energy that ionizing radiation deposits to a volume of tissue.

Ionizing radiation is harmful to all tissues, malignant or healthy. In clinical practice, lethal tumor doses are not always achievable because of radiation-induced morbidity to normal tissues.1 Radiation therapists aim to maximize dose (and damage) to the target tumor and minimize radiation-induced morbidity to adjacent healthy tissues. This is generally achieved by targeting the beam to the tumor area through paths that spare nearby critical and radiosensitive anatomic structures; selecting multiple fields that cross in the tumor area through different paths, to avoid overexposing the same healthy tissues (as would be done by using a single field); and by partitioning the total dose in fractions (small amounts) over successive sessions. Because healthy tissues recover better and faster than malignant ones, with each radiotherapy session the accumulated cellular damage in the targeted tumor increases, while normal tissues are given the opportunity to repair.

Appropriate targeting of the beam is particularly important for tumors that are anatomically adjacent to critical body structures. To date, advances in imaging and radiation treatment planning technologies allow much more precise targeting of radiation therapy, compared to earlier years.1 Apart from conventional external radiation therapy, several modalities have been developed that for radiotherapy delivery. The most advanced method for the delivery of high radiation doses with photon beams is intensity modulated radiation therapy (IMRT). IMRT delivers conformal radiation to the target tumor, by “crossing” multiple properly shaped beams of various intensities through paths that spare radiosensitive and critical adjacent tissues.2 (The intensity of the beam expresses how many photons traverse a given area of tissue at a unit time.) IMRT and other radiotherapy delivery methods (i.e., conventional radiotherapy, stereotactic radiosurgery with photons and brachytherapy) are further discussed in the Results section of this Technical Brief.

Charged Particle Beam Radiotherapy

An alternative treatment modality is charged particle radiotherapy, which uses beams of protons or other charged particles such as helium, carbon or other ions instead of photons.1 As illustrated in Figure 1, charged particles have different depth-dose distributions compared to photons. They deposit most of their energy in the last final millimeters of their trajectory (when their speed slows). This results in a sharp and localized peak of dose, known as the Bragg peak.

Figure 1. Depth-dose distributions for a spread-out Bragg peak of a particle beam for a single entry port.

Figure 1

Depth-dose distributions for a spread-out Bragg peak of a particle beam for a single entry port. The red line illustrates the dose distribution of a spread-out Bragg peak (SOBP) of a particle beam. The SOBP dose distribution is created by adding the contributions (more...)

The initial energy (speed) of the charged particles determines how deep in the body the Bragg peak will form. The intensity of the beam determines the dose that will be deposited to the tissues. By adjusting the energy of the charged particles and by adjusting the intensity of the beam one can deliver prespecified doses anywhere in the patient’s body with high precision. To irradiate a whole tumor area, multiple Bragg peaks of different energies and intensities are combined (Figure 1).

As with photon therapy, the biological effects of charged particle beams increase with (absorbed) radiation dose. Because charged particles interact with tissues in different ways than photons, the same amount of radiation can have more pronounced biologic effects (result in greater cellular damage) when delivered as charged particles. The relative biological effectiveness (RBE) is the ratio of the dose required to produce a specific biological effect with Co-60 photons (reference radiation), to the charged particle dose that is required to achieve the same biological effect. The (general) RBE of protons is approximately 1.1.3 Heavier particles can have different RBE and dose distribution characteristics. For example, carbon ions were reported to have an RBE around 3 in several tissues and experiments.4

Because of these physical characteristics of the charged particle beams it is possible to cover the tumor area (in lateral dimensions and depth) using a single radiation field (something that is not possible with photon beams).1 In general, a set of charged particle fields achieves dose reduction to uninvolved normal tissues, compared to photon radiotherapy. In practice, more than one entry port may be required with charged particles, especially when it is important to achieve adequate skin sparing. We discuss advantages and the disadvantages of charged particle therapy and other radiotherapy options (e.g., external radiotherapy with photons and brachytherapy) in a specific section in this Technical Brief.

Ongoing research explores even more advanced methods to deliver charged particle beam radiotherapy. For example, intensity modulated proton therapy, or IMPT, is a methodology that uses a narrow proton beam (a “pencil” beam) that is “scanned” over the target volume by means of a magnetic field, while both the energy (speed) of the protons and the intensity of the beam are modulated. As of this writing, only the Paul Scherrer Institute (PSI) in Switzerland has facilities that deliver IMPT.

Statement of Work

The Agency for Healthcare Research and Quality (AHRQ) requested a Technical Brief on the role of particle beam radiotherapy for the treatment of cancer conditions. More specifically, the following key questions were defined by AHRQ after discussions with the Tufts Medical Center EPC:

Key Questions

Key question 1

  • 1.a. What are the different particle beam radiation therapies that have been proposed to be used on cancer?
  • 1.b. What are the theoretical advantages and disadvantages of these therapies compared to other radiation therapies that are currently used for cancer treatment?
  • 1.c. What are the potential safety issues and harms of the use of particle beam radiation therapy?

Key question 2

  • 2.a. What instrumentation is needed for particle beam radiation and what is the Food and Drug Administration (FDA) status of this instrumentation?
  • 2.b. What is an estimate of the number of hospitals that currently have the instrumentation or are planning to build instrumentation for these therapies in the US?
  • 2.c. What instrumentation technologies are in development?

Key question 3

Perform a systematic literature scan on studies on the use and safety of these therapies in cancer, with a synthesis of the following variables:

  • 3.a. Type of cancer and patient eligibility criteria
  • 3.b. Type of radiation, instrumentation and algorithms used
  • 3.c. Study design and size
  • 3.d. Comparator used in comparative studies.
  • 3.e. Length of followup
  • 3.f. Concurrent or prior treatments
  • 3.g. Outcomes measured
  • 3.h. Adverse events, harms and safety issues reported


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