You're talking one trial. Take the very long view (see below). But no, I thought they'd be equal. That they were not in one 3-arm trial: them's the statistical breaks (again, see below). I don't think there's a deep understanding necessary. Throw some live cells in a dish. Irradiate them. Plot the cell death rates on a graph. Devise an equation that best fits the curve. Try to explain the curve ("I can irradiate cytoplasm, cell lives; I can irradiate nucleus, cell dies... there's DNA in a nucleus", "If I change dose, death rate changes... although non-linearly" etc etc). Correlate macroscopic clinical outcomes to the microscopic cell death rates when/if possible. I don't think you can really compare toxicities (that well) between trials, or any outcomes for that matter. But you can get a gestalt. I don't think CHHiP was a home-run and HYPRO a strike-out. If you believe in CHHiP you ought to more or less believe in HYPRO fractionation too... Let me throw out a few random observations, 'cause we might be talking past one another. You can pick apart each observation individually; might make things simpler. 1) I have no major reservations re: toxicity for hypofractionation in any circumstance, prostate included. My worries are niggling at best. We've all mentioned these niggling concerns. 2) Standard fractionation was an established standard of care for prostate CA antecedent hypofractionation. Clinically speaking, standard fractionation is an excellent treatment for prostate cancer. Financially speaking, it is more expensive. Time-wise, it takes more days of treatment. These are standard fractionation's only drawbacks (time, money) vs hypofractionation. 3) On paper, and in theory, things like 70/28, 60/20, ~64/19, etc., and even 81/45, show equivalence. 4) In practice and in studies, things like 70/28, 60/20, ~64/19, etc., have not necessarily shown equivalence. This should surprise no one, nor does it invalidate the fact that on paper/in theory they're equivalent. I say 60/20 and ~64/19 are equivalent. If you run a trial of 60/20 vs standard and another trial of 64/19 vs standard and get different results--this is just statistics at work, not a failure of the BED model per se ("our understanding is not as good as the radiation biologists would have you believe"). One can expect that a similarly-styled study will replicate the results of a previously positive study about 50% of the time... meaning in essence that the positive study (if you cite ONE study) you cite had about a 50% chance of being negative when it was run. In other words, the study you cite w/ p<0.05 has a coin's flip chance (or less) of being "truly positive." (This is one of the greatest "inconvenient truths" in oncology.) One of the main reasons for this is that the p-value of 0.05 may be too high; a p-value of 0.005 may be needed (in an alternate universe, this is the p-value everyone would use.) E.g., in CHhIP, "60 Gy was non-inferior to 74 Gy (HR 0·84 [90% CI 0·68–1·03], pNI=0·0018)." And this wasn't even a 95% C.I. Were a 95% C.I. used, 60 Gy would have been not non-inferior at p>0.005. At 99% C.I., I bet the p-value would have been >0.05. Is this important? I wonder. Am I skeptical? Yes! Is this solipsism? Gosh I hope not or I don't understand words... I am pretty sure your "solipsism" here is another -ism... a malapropism. Certainly never meant to convey that nothing exists beyond the confines of my own thoughts/mind; I want to look at all the data and everyone's experience. Perhaps you meant "sophistry." I can't know your mind. Either way, one is at risk for solipsism and/or sophistry if one has an active, skeptical, free-ranging mind, and private practice is neither the sole bastion of either sophistry nor mendacity IMHO. It borders on mendacious to throw away with abandon decades of established standards of care which also indirectly shames those involved in delivering those accepted standards of care over the previous decades... especially when the clinical signals from hypofractionation in certain settings have not been uniformly clear and/or beyond-statistical-reproach clear. Let's be non-mendacious: if, given the clinical results of all the hypofractionation trials, hypofractionation cost twice as much as standard fractionation, would anyone do hypofractionation? Of course not.