Delivering energy to the tumor.
The goal of any cancer therapy is to destroy the malignant cells in the body while doing minimal damage to the healthy tissue. Modern cancer therapies, no matter if they are chemotherapy, targeted medications, surgery, X-ray therapy, or particle beam therapy, are all about collateral damage: destroy the cancer but not the patient.

Whenever the malignant cells are confined in a geometrically identifiable volume (the tumor) the preferred therapy is surgery and/or radiotherapy, often in combination with chemotherapy in a support function. In those cases where surgery is not possible or advisable due to the location of the tumor or the overall health condition of the patient, radiotherapy is the method of choice. Roughly half of all cancer patients receive radiotherapy as primary or supportive therapy during the course of their treatment

In radiotherapy energy is deposited to the tumor volume to harm the cancer cells in form of ionizing radiation. This can be done internally by implanting radioactive seeds in the tumor (brachytherapy) or externally by aiming beams of X-rays or gamma rays (generally called photons), or heavier particles like protons and ions at the tumor.

	Fig. 1: Patient positioned for X-ray treatment at a linear accelerator.

X-ray therapy:
Photons beams easily penetrate the human body. Theydeposit most of their energy near the skin level and then in a slowly decreasing manner all the way to the exit on the other side of the body. (see figure 2). The ways of differentiating between the tumor and the healthy tissue often is based on the decreased repair efficiency of tumor cells compared to healthy cells. To exploit this difference in repair capability of malignant and healthy cells the total amount of energy is administered in fractions of typically 2 Gy per treatment and spread over several weeks. In between individual treatmentshealthy cells can repair the damage inflicted by the radiation received and recover while the tumor cells are unable to totally overcome the damage inflicted. Over time the healthy tissue wins over the tumor.

Conformal radiotherapy and IMRT:
To reduce the amount of ionizing radiation received by the healthy tissue one can use several beams of lower intensity aimed at the tumor from different directions. These beams overlap at the tumor site to deposit an amount of energy to the cancer cells which is much higher than what the healthy cells outside the tumor volume receive from the individual beams. In 3DCRT (3 dimensional conformal radiotherapy) individual beams are shaped by collimators to conform to the shape of the tumor seen from a beams eye view. An enhancement to 3DCRT is IMRT where not only the shape of the beam is controlled but also the intensity of the beam is varied across its area by using dynamic multileaf collimators. IMRT improves the doctor’s ability to conform the treatment volume to a complex shaped tumor, especially in cases where the tumor is partially wrapped around a vulnerable structure like the spinal cord or a sensitive organ and therefore has a concave shape.

The next step: particle beam therapy.
Still, even with these modern techniques one cannot beat the basic laws of physics; even in the most advanced forms of IMRT the total amount of energy delivered to healthy tissue is higher than the energy delivered to the tumor – it is only spread over a larger volume.
Another problem inherent to photon treatments of any type is the fact that photons deliver energy to tissue in front AND BEHIND the tumor. This is entirely different for heavier charged particles, like protons, ions, (and antiprotons).

Fig. 2: Comparison of dose distribution for X-rays and particle beam therapies. The pink box depicts the tumor located some distance in the body, the red curve shows the dose distribution using heavy charged particles, and the black curve shows the effect of X-rays. The yellow area shows the unnecessary irradiation of healthy tissue in front and behind the tumor.

As Robert R. Wilson described in his seminal paper of 1946, heavy charged particles like protons and ions have an entirely different way of depositing energy. Initially, when they enter the body they do very little damage, even though they are continuously slowed down by the electric forces between the charged projectiles and the charged particles in the atoms of the body. Depending on the initial energy (velocity) when entering the body they can travel only a certain distance before they come to a stop. And that is where they deposit most of their energy. This stopping point can be dialed in very precisely by choosing the initial energy of the beam and can be targeted precisely at the tumor. Compared to photon therapy the amount of energy deposited to the healthy tissue in front of the tumor is smaller and there is no energy deposited to the cells beyond the tumor. The energy delivery in particle beam therapy is concentrated on the target region and the energy delivered to healthy tissue is much reduced compared to the case of photons (X-rays) (see figure 2).  

Since the beginning of the last century physics was the dominant driver in providing improvements to radiotherapy. The development of photon sources with higher and higher energy lead to better dose distribution at each step, which in turn allowed lower dose to the healthy tissue and therefore lower toxicity of the treatment. The latest improvement in physical dose distribution has been the invention of proton therapy which offers a dramatic change in dose conformity to even very complex tumors.

As you can read on the pages about carbon ion therapy and antiprotons we have now reached a point in time where biology has been brought back into the field again in order to further enhance the power of these new treatment modalities. As ions and antiprotons have a distinctively different effect on cells, these methods will allow targeting tumors which have so far evaded the attack by photons and protons, and therefore have been called ‘radioresistant’.

Fig. 3: 100 years of advances in physics have led to continuous improvements of the dose distribution. Higher photon energies have led to lower dose to healthy tissue, which has reduced the toxicity of the treatment, and thereby led to better tumor control and higher patient survival. The introduction of protons have continued this tradition, but really in a form of a quantum leap. (The years are giving the time when these methods became available in clinical settings.)

A good general summary of radiotherapy (not including particle therapy) can be found on Wikipedia (http://en.wikipedia.org/wiki/Radiation_therapy). To learn more about different levels of particle therapy, please visit the individual subsections on proton therapy, carbon ion therapy, and on the groundbreaking research and the early developments towards antiproton therapy.