Brane Space: Improving Proton Beam Therapy For Better Cancer Treatment

Comparing degrees of localization of proton beam therapy with other treatment modalities, in terms of dose v, tissue depth.

The basis of 'momentum cooling' for proton beam therapy

I (briefly) considered getting proton beam therapy when my prostate cancer was first diagnosed back in July, 2012. However, my wife (a former radiotherapy software specialist) convinced me that high dose rate brachytherapy - which her company specialized in - was the better option. Plus, she knew the best center in the nation to get it: the Helen Diller Cancer Center at University of California - San Francisco and had worked with the world-famous oncologists there . She was also skeptical proton beam centers existed that could give 100 percent assurance and confidence that through all the 30 or so days of treatment one would not see a "geographical miss". That is, the proton beam hitting a critical region like the bladder or lower bowel instead of the cancer, putting an unwanted micro-hole in either.

For those not aware, proton beam treatment is a form of external beam therapy in which positively charged particles (protons) are accelerated to 60 percent of the speed of light, or 180,000 kilometers per second. They are constrained to form a powerful beam that can be programmed to deposit most of its energy directly into a target tumor - say in the prostate gland - minimizing radiation exposure to surrounding healthy tissues (say bladder and lower bowel in the case of prostate tumors)

As seen in the graphic at top, x-rays still remain the tool for most radiotherapy. They deposit their energy everywhere along their path in tumor and healthy cells alike. Hence, the potential for averse side effects. Protons, by contrast, have scattering cross sections that depend inversely on their kinetic energy. So a proton passing into tissues slows down in increments and leaves most of its energy right before it stops. By controlling the beam's direction and initial kinetic energy clinicians can position the radiation-affected region in all 3 dimensions.

In practical terms, however, controlling proton kinetic energy is not so simple. Clinicians and oncologists basically need proton energies ranging from 60 Mev - for tumors close to the body's surface- to 230 Mev for tumors tens of centimeters deep. Problem is that a single cyclotron produces proton beams at just one energy and it would be exorbitantly expensive to have a cyclotron for every energy needed. Most proton therapy centers use cyclotrons at the top of the energy range, 230-250 MeV, but this is where the greatest inefficiency enters.

True, one can turn high-energy protons into lower-energy protons by passing them through a chunk of solid material, usually carbon. But the energy-degradation process also turns a monoenergetic proton beam into one with a considerable energy spread—no longer suitable for clinical use, because the protons’ localized depositions of energy, known as Bragg peaks, are no longer all in the same place. The standard approach is to use a dipole magnet to disperse the protons by energy and then pass them through a slit to select protons with as close to a single energy as possible. Most of the protons, as a result, are thrown away.

The waste is worst at low clinical energies. The more the cyclotron protons need to be degraded, the larger their energy spread, and the lower the fraction transmitted through the energy-selection slit. For target energies greater than 200 MeV, perhaps 10% or more of the initial protons can be salvaged. But for target energies less than 100 MeV, less than 1% can.

Existing ion-optics setups treat the two dimensions perpendicular to the beam symmetrically, and they apply the same focusing and defocusing forces in both directions. But the dimensions aren’t symmetrical—in part, because the protons are dispersed by energy in one direction but not the other. It turns out that recent research by V. Maradia et al (1, 2) has shown that by accounting for that asymmetry, they could improve transmission by up to a factor of six.

There remains the greatest source of inefficiency: the protons discarded at the energy-selection slit. The solution, it turned out, was deceptively simple. The protons were already dispersed by energy, and their momentum can be slowed by passing them through solid material. So Maradia et al proposed sticking a wedge into the beam, as shown in the lower graphic at top of post. from a cyclotron are tuned to the energies required for proton-beam therapy, they end up with a momentum spread p ± Δp that’s too wide for clinical use. The conventional approach is to use a dipole magnet (dark blue) to disperse the protons by momentum and then pass them through a slit to select out the protons with just one momentum value, p.

But if, instead, a wedge-shaped absorber is used to cool all the protons momentum to p – Δp, more protons can make it through the beamline and into the patient. Long story short, Maradia came up with the momentum-cooling idea on his own, but he noticed afterward that wedge-shaped absorbers had been used before in other areas of particle physics, such as muon experiments.³ To be sure muons had not been considered before for proton therapy, perhaps because when the protons scatter off the wedge, their momentum spread perpendicular to the beam increases. But Maradia and colleagues’ improved ion optics were equipped to handle the increased spread.

The results have been positive but modest: From an initial fraction of 0.27% of protons, the wedge increased transmission almost twofold, to 0.5%. Why such a small improvement? The beamline as a whole was designed on the basis of the assumption that only protons with one specific energy would ever make it through to the patient. After being dispersed by the dipole magnet, most of them collide into the beamline walls before they even reach the wedge. If the dipole magnet deflected the protons at a shallower angle, the loss could be mitigated, and the researchers estimate that transmission at the lowest energies could be boosted to perhaps 7%. Making such a change to an existing beamline is probably not feasible. But according to Maradia it would be relatively easy to incorporate momentum cooling into future proton-therapy centers.

Alas, all these improvements would simply be too long in coming to have any benefit to me now, though my urologist has proposed the nanoknife as a radiotherapy option to deal with further metastasis. The problem is that this procedure entails general anesthesia and I have already suffered significant memory dropouts from three administrations of such over 18 months in 2016-17, see e.g.