Heavy Ion Therapy
The ultimate precision of heavy ions:

Early in the development at the Lawrence Berkeley National Laboratory Robert Wilson and colleagues realized that heavier charged particles, like Helium, Argon, and Neon may have significant advantages for the use in cancer therapy compared to the standard particle, the proton. Just like protons heavy ions show the distinct feature of the Bragg peak as the dose increases along with the penetration depth into the body, culminating in a sharp maximum at the end of the particle range. As the particles get heavier, they are less affected by collisions on the way to the tumor and the beam does not spread nearly as much as in the case of the lighter protons. And not only is the beam confined better in radial direction, the Bragg peak itself is also a lot sharper than for protons (see figure 1). This leads to still higher precision in treating tumors in sensitive areas of the body.

Increased Biological Effectiveness:
There are more advantages to be considered. Heavier particles have a bigger effect on the atoms in the body and can do more damage on the scale of individual cells. Simply put, there are damages which can be inflicted by X-rays and protons which can be repaired by the natural healing mechanism of the tumor cells but when a heavier particle hits the same cell, the damage is more severe and the cell has no chance of recovering.

As a result the biological effectiveness of heavy ions is larger than for X-ray and protons. In radiology one arbitrarily defines the relative biological effectiveness (RBE) of a radiation type as the ratio of energy (dose) needed for an X-ray treatment using a Cobalt-60 source to inflict the same damage as when using this new type of radiation under study. RBE is a complex concept and the exact number depends on many details of the study, including cell type, definition of damage to be studied, and many other things, and one must be careful when making quantitative statements on this issue.

In general protons and X-rays have pretty much the same effectiveness and for the purpose of treatment planning in therapy the RBE of protons has been defined as 1.1 throughout the flight path. The RBE for heavier ions varies along the path towards the Bragg peak and can reach values as high as 5 – 10 towards the end of range.

Picking the right ion:
The increased RBE means that heavier ions are an ideal tool to treat those tumor types which have been found to have strong repair capabilities and have therefore been called ‘radio resistant’ as they can repair damage done by x-ray (and proton) radiation. Initial studies using heavy ions were done at Berkeley concentrating on Helium, Argon, and Neon ions. But it turns out that Mother Nature really has meant Carbon ions to be the magic bullet. Why is that? We said above that the RBE increases with penetration into the body; we also know that the dose deposition increases with depth, but only in the case of carbon ions these two increases go hand in hand. If we look at heavier ions the RBE is already high before we reach the Bragg peak, causing an undue amount of biological damage in the healthy tissue; if we use lighter ions (like helium) the RBE is still around 1 when we reach the Bragg peak and only increases significantly at the distal edge of the peak, where the dose has already dropped sharply.

Carbon ions – the magic bullet:

Carbon ions combine excellent physical properties with biological advantages. The lateral scattering at 10 cm depth in the body is only 1 mm and the Bragg peak is much sharper than for protons. In addition, the biological effective dose increases more rapidly with depth than the physical dose due to the increase in biological effectiveness. This means that for a given biological dose the load to the healthy tissue to the tumor is reduced significantly. Therefore the ratio of desired damage in the tumor to the undesired - but unavoidable - damage inflicted on the healthy tissue (the ‘therapeutic ratio’) is increased. This allows the radiation oncologist to reach higher tumor dose, and therefore better tumor control, for an equal low effect on healthy organs when using carbon ions instead of protons. Therefore carbon ions have become the preferred modality for treating brain tumors, tumors at the spinal cord, and many other indications where utmost precision or minimal impact on healthy tissue is required.

Fig. 2: A dose plan for a carbon ion treatment of a brain tumor. The high precision allows complete sparing of the brain stem marked by the green line. (Image from G. Kraft, GSI

Looking inside the patient:
This is still not all! There is one more benefit to the heavier ions: On the rare occasions of a collision during their flight towards the tumor they can break up into fragments which are radioactive and emit positrons (the antiparticles to electrons). These positrons can be detected using the well established technology of Positron Emission Tomography (PET) to generate an image of the exact dose distribution delivered to the patient. This is an important tool in cases where the particle beam has to traverse complex structures in the body where the exact density is not always known. As an example, the three frames in the figure below show from left to right a planned dose distribution for a brain tumor, the positron activity calculated by a computer for this specific dose plan, and finally the measured positron activity. The fact that the last two frames are nearly identical proofs that the planning study was using the correct densities for all materials the beam was traversing. A deviation would be easily detected and could be corrected before the next session.

Fig. 3: Example of imaging of a dose distribution using positron emission tomography. The near perfect agreement of the middle and the right frame confirms the correctness of the dose plan applied. (Figure from Enghardt, W. et al, Strahlenth. Onkol. 1999, 175, Suppl. II, 33-36)