It's a good post......but, I think it reinforces my general concerns about directly ionizing therapeutic radiation.
First, the time frame of ion therapy. Many aren't aware exactly how old this technology is. Parallels big center particle physics as it emerged in mid 20th century. Ion therapy is old.
The enthusiasm for ion therapy was most justified in the era that preceded the invention of the CT scanner. When therapy was in fact delivered by 1 or 2 beams only with lots of anatomic uncertainty (and photons at Cobalt energies). The energy deposition curves alone would be a remarkable cause for enthusiasm in that era. Those days are long gone, however.
The CT scanner eventually brought with it very high quality, volumetric dosimetry. The interactions of indirectly ionizing photons with living tissue are pretty well understood, and I would argue that we now live in an era where photons can be delivered through a maximum solid angle over minutes, with modulation optimized by millions of iterations, and with a dosimetric certainty (as it effects biologic outcomes) on the order of 5%.
Nothing like this exists for directly ionizing therapy, and it may never exist. As a charged particle slows, it's interactions with living tissue may vary remarkably. It could almost be considered an Uncertainty Principle type of problem. The rest mass of ions that lets them stop abruptly in space, confers highly variable interactions even with subtle changes in the matter that it is interacting with. In other words, we can know their final position with greater certainty than photons (hence the bragg peak) but we lose certainty regarding true BED.
CT scanners helped photons a ton. MRI helps some. These thing cannot help ion therapy to the same degree.
You are correct.
A major variable in particle therapy is RBE, especially normal tissue RBE, at least on the individual patient level. On the macro/population level, I think over 20,000 patients have now been treated and it works in general for tumor control. There is talk of a randomized trial of sorts in the works for prostate cancer, I think with Mack Roach, Xrays and protons and carbon. In the US, patients would get proton or Xrays, in Japan, carbon or Xrays, I think. Patients in the US will not be randomized to receive a flight to Japan, but actually I think that would help enrollment - I'd like to go see Asia anyway.
Interestingly, Heidelberg is taking a step back from carbon ion and has started treating patients with helium ions. For pediatric patients in particular, the lower entrance RBE of helium ions in normal tissues leading up to the tumor is seen as a potential advantage.
One of the nice things about helium ions is that they have lots of radiobiological data from all the years of alpha particle research, which behave basically the same as the helium ion Bragg peak.
RBE is cooler in the entry zone for helium than carbon ions; the entry RBE for carbon is 1.5 with a rapid rise to 3-4, plus the fragmentation tail of smaller particles as the carbon nucleus breaks apart into boron, beryllium, lithium, helium, deuterium, protons, neutrons, etc. The carbon ions stop on a dime, but its fragments travel a bit further before stopping.
Helium ion's entry RBE is 1 near the skin surface with a delayed rise to 3-4 at the Bragg peak. I've seen comparison plans between carbon and helium where I cannot tell the difference.
