3 Comments

Amazing thoughtful insightful article. ASTRO (and ACRO) should have you directly involved in Proton committee leadership.

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Thank you for the kind words. Obviously living in the weeds on this one, but if 10 people around globe consider things differently, then job is done.

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Sorry, but I'm still trying to get clarity on exactly what the prescriptions would be.

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within the new model, the dose to the patient needs to remain the same, but use the model, not to reduce the dose to normal OARs, but to increase the deposition of dose within the target. So in this scenario, we might push the mean target dose from 6000 to 6400 using the optimized non-linear model.

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If the physical/absorbed (not BED) doses don't change, the only thing that could be different would be LET optimisation (how the physical dose got to the voxel).

If you are saying "the dose to normal/OAR should stay the same", and if we can assume that they won't be near the Bragg Peak, then it's both the physical dose and the BED staying the same for normal/OAR. You would either have to have a "better plan" where you keep the Normal/OAR but get more physical dose to the tumour, or you've done LET (and RBE) optimisation (which is a better plan under the assumption being tested).

If you are allowing the mean target dose to go as high as 6400cGy(RBE), then it's an LET/RBE optimised plan with a loose upper constraint on mean dose (BED) to tumour (>6000 cGy(RBE), weak or no constraint up to 6400 cGy(RBE)) with a fixed upper bound on on the OAR/Normal to match non LET/RBE optimised plans. Maybe I'm getting tripped up on the original statement of the prescription (

("6000 cGy(RBE)" rather than "minimum of 6000 cGy(RBE) but iso-toxic with the non-optimised plans".

Although they may not be taking the data, aren't people kind of already doing this with LET optimised plans (they also aren't calculating the BED based on those LET optimisations)? They might be doing this with the idea that they are avoiding placing the high LET dose in OAR, but when looking at sample plans, I always see the high LET region being put *in* the tumour.

I think the (probably too) bold move would be to do an LET/RBE optimised plan but keep the mean dose (BED) to tumour to see if there is lower toxicity. I guess it depends: What is the bigger clinical issue right now, lack of success in control or too high toxicity? If (big if) there's great control and low toxicity, it might be close to Pareto optimal already.

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