ProPublica Picks Protons

[RickyScott]

Im not a proton person and I don't actually think the logic for pancreas will pan out but theoretically it is at least conceptually not that different from what we are doing. The logic is with the higher BED you can try to dose escalate as much of the GTV as possible. For all the reasons stated, you would have to accept lower dosing to the margins but in fairness, that is what we do with most of the MRI-guided SBRT or Crane style dose escalation approaches. They are essentially dose-painted plans to get as much of the GTV as safely possible to a high dose. Its potentially doable with protons but will it be better? I doubt it. I like dose escalated SBRT because its generally very well tolerated and works at least as well if not a little better than conventional fractionation. But people still recur and progress. It has not been as game changing as I had hoped and I don't see protons doing any better. I think PNI and marginal sparing (which is necessary) limit how much we can accomplish with any dose escalation techniques.

agreed but the biological effect of dose at the edge of the ptv seems much more damaging/unknown bed/large effects by slight changes in set up certainty, breathing with protons.

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[Upgrayedd]

it seems protons are never a good idea when ptv immediately adjacent/overlap with critical structures (prostate/pancreas).

I would suggest a slight modification to this:

1. It seems when the GTV directly abuts a critical structure protons alone do not add value and may be deleterious (prostate/pancreas/posterior fossa/central lung/some H&N).
-> Note - PTV under coverage is very reasonable; as @ramsesthenice notes above; w/ Crane/Ablative style panc dosing and OAR PRV prioritization.
2. When the PTV abuts a low Z medium (i.e. chest wall ranging into low-z lung), your integral dose could be worse than a photon plan
3. As such, protons add value only in very specific settings for sparing organs in parallel. They do not add value for sparing organs in series and may actually harm these organs due to RBE uncertainty and lateral penumbra. This contradicts much of the original proton dogma. Q.E.D.

Someone above commented about why does the distal most Bragg peak matter? It is because it is the only "pristine" Bragg peak in a Spread Out Bragg peak. It has full physical dose (100%) because its leading edge does not overlap with the tail of any other peaks, and so its RBE is "undiluted", you get the full 1.3 to 1.5 Gy in the normal anatomy beyond the PTV.

Ideally you want that high RBE only in the GTV, which is possible with IMPT but not passive scatter. I will sometimes try to "trick" the optimizer into doing this by creating an SIB

@IonsAreOurFuture - I understand what you are saying; but honestly I am not sure you full understand the what is going on w/ the SOBP and the summation/integral of the downrange dose. If you look at a lot of the physics work from the 2018 (I think?) ASTRO special session on brain stem necrosis; LET and RBE uncertainty, and ways to mitigate it (many of which you address). Your point about a "pure" Bragg peak just does not make sense in regards to the clinical sequalea.

Correct me if I am wrong; but what I imagine happening is similar to how an electron beam creates downrange atomic interactions and builds a fluence/flux of photons that builds up to a asymptotic level over depth.

The crux of the Proton "problem" is that instead of a fluence/flux of photons, it includes a flux of subatomic particles with directionality and energy; and whose RBE is difficult to calculate and/or model; and whose ultimate penetration does not map onto the proton range.

A Bragg peak in the middle of a SOBP mathmatical distribution (i.e. one in the GTV) as you describe; one in which is weighted less than the distal-most Bragg peak; would still possess all the same qualities of the distal Bragg peak (generating the equivilent of subatmoic shotgun blasts of potentially high RBE subatomic buckshot); but with an x% multiplier given the dose at that point is a sum of the different energies. It would still participate in the Asymtotic build-up of flux. We just don't notice that as much since it gets adjusted for in the Proton RBE multiplier and/or it is in the GTV; but it most likely participates in the lateral beam uncertainty/penumbra.

As such; I would propose the "problem" of protons is inseperable from the technology. Unless better mapping/modelling is generated.

Robustness can help but it is an inherent source of error/uncertainty.

 

[drowsy12]

Im not a proton person and I don't actually think the logic for pancreas will pan out but theoretically it is at least conceptually not that different from what we are doing. The logic is with the higher BED you can try to dose escalate as much of the GTV as possible. For all the reasons stated, you would have to accept lower dosing to the margins but in fairness, that is what we do with most of the MRI-guided SBRT or Crane style dose escalation approaches. They are essentially dose-painted plans to get as much of the GTV as safely possible to a high dose. Its potentially doable with protons but will it be better? I doubt it. I like dose escalated SBRT because its generally very well tolerated and works at least as well if not a little better than conventional fractionation. But people still recur and progress. It has not been as game changing as I had hoped and I don't see protons doing any better. I think PNI and marginal sparing (which is necessary) limit how much we can accomplish with any dose escalation techniques.

The point is that it’s MORE doable with photons than proton. Proton has a disadvantage of high dose gradients. It simply can’t do what a tight tight VMAT plan can. Hence the question of why it would make sense?

Proton helps with low dose fall off. But that’s not the dose limiting issue in dose escalation in pancreas cancer. It’s the adjacent duodenum.

Again my friends at high volume proton centers have told me this themselves. Also it’s pretty much common sense understanding of proton vs photon, so I look forward to Ions’ explanation.

I hope that VMAT proton happens eventually, then it may be diff story

 

[communitydoc13]

3. As such, protons add value only in very specific settings for sparing organs in parallel. They do not add value for sparing organs in series and may actually harm these organs due to RBE uncertainty and lateral penumbra. This contradicts much of the original proton dogma. Q.E.D.

Perfect...thank you.

One must accept a different level of dose uncertainty with protons (or any charged particles, including electrons) than with the very, very dumb high energy photons that most of us use for therapy.

The crux of the Proton "problem" is that instead of a fluence/flux of photons, it includes a flux of subatomic particles with directionality and energy; and whose RBE is difficult to calculate and/or model; and whose ultimate penetration does not map onto the proton range.

I'm not sure about lack of mapping onto proton range? Stripped electrons are going to show up with water dosimetry experiments pretty well. I think that the actual dose (in a biologically meaningful way...BED) at the end of a proton's journey (where density of interactions becomes quite high) is just not well modeled period and is likely very sensitive to the electron environment present (this is chemistry and biology). Range straggling is pretty well understood by statistical factors regarding variation in number or interactions along a beam path.

I think an analogy to a photon that loses energy along its beam path is a valuable one. (This does not happen, but imagine that it did). The photons start out energetic and dumb with pair production, Compton scattering and Rayleigh scattering as dominant interactions as the photon becomes less energetic. These interactions are not terribly discriminating (thus dumb). However, as the photon loses more energy, photoelectric effect becomes dominant, and this is much more discriminating...get even less energetic and you are in the UV domain and smart as hell, causing pyrimidine dimers and such...now working in the domain of biology.

It is because it is the only "pristine" Bragg peak in a Spread Out Bragg peak. It has full physical dose (100%) because its leading edge does not overlap with the tail of any other peaks, and so its RBE is "undiluted", you get the full 1.3 to 1.5 Gy in the normal anatomy beyond the PTV.

I think what Ion is saying here is that at the very distal aspect of the dose/depth curve, the only contribution is from very slow protons and their associated interactions. Any point less deep is going to have contributions from both very slow and faster protons, where the interactions for faster protons (with fewer interactions per unit space) seems to be better modeled.

But...the peak of the bragg peak is mostly protons coming to a stop and is also where peak dose is delivered. The total BED uncertainty at the peak may still be greater than at the far end of bragg "hump" because total dose here is higher.

Anyway...the original proton dogma (I don't know what this was, but I do know Jim Cox's dogma circa 2007) was criminal.

 

[Upgrayedd]

I'm not sure about lack of mapping onto proton range? Stripped electrons are going to show up with water dosimetry experiments pretty well.

I was thinking neutrons at least.

I think what Ion is saying here is that at the very distal aspect of the dose/depth curve, the only contribution is from very slow protons and their associated interactions.

Good point, it certainly does give some credence to what Ions is saying.

So is the answer that you build up the distal edge of a proton beam with another tangential proton beam with a higher contribution of fast protons? If so; I’ll admit I may be wrong; but I would advise the proton folks to phrase it more clearly.

Of course data on the safety of this would be good too.

 

[ramsesthenice]

The point is that it’s MORE doable with photons than proton. Proton has a disadvantage of high dose gradients. It simply can’t do what a tight tight VMAT plan can. Hence the question of why it would make sense?

Proton helps with low dose fall off. But that’s not the dose limiting issue in dose escalation in pancreas cancer. It’s the adjacent duodenum.

Again my friends at high volume proton centers have told me this themselves. Also it’s pretty much common sense understanding of proton vs photon, so I look forward to Ions’ explanation.

I hope that VMAT proton happens eventually, then it may be diff story

Don't ask me LOL. I, like you, am not convinced it will be better, or that the RBE difference will really allow so much dose escalation that it will make a clinical difference even if the gradient issue can be addressed. But if the high volume folks who know what they are doing want to give it a try, I'll wait for the data. I've been wrong a lot before.

 

[ramsesthenice]

No offense to Ions or any of the folk here who I genuinely believe to be reasonable professionals, but yesterday I had one of those WTF interactions that reminded me of the unfortunate protoplasm that exists in certain specters of the proton world. Met with a dude who had an in-gland recurrence after prior proton therapy at a center outside of my region a while back. Told me his proton doctor told him that since they used protons and his normal organs were spared, repeat radiation would be no problem (eye roll). When I started talking about risks of any salvage approaches, including bleeding and need for HBO or diversion, he piped up and said "I had to do that oxygen thing last time because of bleeding. My doctor told me if they hadn't used protons, I probably would have needed a bag." (vomit in mouth) I don't care if it's protons, MRaRT, or good ole' fashion IMRT, f****** own up to it when something goes wrong and don't BS your patients.

 

[winstonfoot5]

so hard to know how this conversation actually went without being present. I try to give the benefit of the doubt to our colleagues... but probably "The true is somewhere in the middle"

 

[deleted1111261]

so hard to know how this conversation actually went without being present. I try to give the benefit of the doubt to our colleagues... but probably "The true is somewhere in the middle"

are you sure? Have you seen the infographics from Maryland and MDACC?

 

[TheWallnerus]

Think about it. It would be too cognitively dissonant—walking into these massive, exclusive pantheons to human and medical progress that we call Proton Centers with a beautiful academic ID badge over one’s heart—to admit that protons haven’t saved every single proton-irradiated patient from a potential photon harm. Elsewise, what the hell would you be working there for?

 

[BobbyHeenan]

No offense to Ions or any of the folk here who I genuinely believe to be reasonable professionals, but yesterday I had one of those WTF interactions that reminded me of the unfortunate protoplasm that exists in certain specters of the proton world. Met with a dude who had an in-gland recurrence after prior proton therapy at a center outside of my region a while back. Told me his proton doctor told him that since they used protons and his normal organs were spared, repeat radiation would be no problem (eye roll). When I started talking about risks of any salvage approaches, including bleeding and need for HBO or diversion, he piped up and said "I had to do that oxygen thing last time because of bleeding. My doctor told me if they hadn't used protons, I probably would have needed a bag." (vomit in mouth) I don't care if it's protons, MRaRT, or good ole' fashion IMRT, f****** own up to it when something goes wrong and don't BS your patients.

I actually had a similar interaction about 5 years ago when I saw an inpatient consult for bleeding proctitis s/p protons (not by me) for prostate cancer. Nearly the exact same sentiment from the patient "imagine how bad this would be if I would have had photons."

The beautiful facilities, pictures of dose clouds, advertising, and good customer service/friendly faces does a lot of heavy lifting regarding patient sentiments.

 

[BobbyHeenan]

Think about it. It would be too cognitively dissonant—walking into these massive, exclusive pantheons to human and medical progress that we call Proton Centers with a beautiful academic ID badge over one’s heart—to admit that protons haven’t saved every single proton-irradiated patient from a potential photon harm. Elsewise, what the hell would you be working there for?

I have developed more sympathy (?is that the right word?) for some of the proton docs over the years...though much of it is "self inflicted." Patients come into the facility basically demanding protons. So then you don't need much nudge to acquiesce. But I can't help but think a big reason they come in there demanding it is the advertising and some of the newspaper/pro publica type reports about the unending benefits.

 

[RickyScott]

I have developed more sympathy (?is that the right word?) for some of the proton docs over the years...though much of it is "self inflicted." Patients come into the facility basically demanding protons. So then you don't need much nudge to acquiesce. But I can't help but think a big reason they come in there demanding it is the advertising and some of the newspaper/pro publica type reports about the unending benefits.

Not docs fault unless total huckster like steve frank. Its not like we have much of a choice where we work

 

[deleted1111261]

I have developed more sympathy (?is that the right word?) for some of the proton docs over the years...though much of it is "self inflicted." Patients come into the facility basically demanding protons. So then you don't need much nudge to acquiesce. But I can't help but think a big reason they come in there demanding it is the advertising and some of the newspaper/pro publica type reports about the unending benefits.

THIS! I am so glad I don't deal with it. Patients demanding specific treatments makes me salty. I also don't have enough time to spend all that cash, so I stick with photons. And not many of them.

 

[TheWallnerus]

I have developed more sympathy (?is that the right word?) for some of the proton docs over the years...though much of it is "self inflicted." Patients come into the facility basically demanding protons. So then you don't need much nudge to acquiesce. But I can't help but think a big reason they come in there demanding it is the advertising and some of the newspaper/pro publica type reports about the unending benefits.

The number one indication for proton therapy in America is breast cancer.

I imagine some women walk in the proton center asking for protons. But I bet many were told by a rad onc protons were best.

In my opinion, every woman asking for protons doesn't need acquiescence, they need education and a refusal to be irradiated via protons.

 

[radiaterMike]

I have never treated a patient with protons ... but I think there could be a justifiable role in with breast (or chest wall) and comprehensive nodal coverage in minimizing heart and lung exposures. VMAT results in a lot of beam entry into the heart and lungs, and fixed beam IMRT does not do as good of a job with conformality with convex/concave targets.

I agree that with typical whole breast RT lowering mean heart and lung doses (on a computer screen) is not clinically meaningful. The NEJM Darby paper analyzed patients treated with antiquated techniques using reconstructed dosimetry (which I don't think is as bad as it sounds since they were very diligent), and the concept of no threshold for mean heart dose is based on a lot of extrapolation.

 

[communitydoc13]

The number one indication for proton therapy in America is breast cancer

The best cases to treat are the ones with overwhelmingly good outcomes regardless of the intervention and patient demographics skewing towards wealth.

A stage I, probably ER+ breast cancer in a patient probably over 60? 15 fractions of protons?

…genius (keep the plan cool and away from chest wall and skin...the competition is offering 5 fraction photons for a pittance).

Collect your cash and your local philanthropic awards.

 

[IonsAreOurFuture]

There are papers out there with hybrid photon/proton plans (eg PMID: 37913953), though this is primarily aimed at NCTP reduction. Photon contribution drops with newer techniques such as arcs. Imagine slow throughput even slower with mixed beam plans would inhibit practicality.

The other impracticallity of combining protons with photons to "merge" the benefits is having 2 machine appts daily for a patient, creating 2 plans, and only getting paid for one. Insurance is not going to give an auth for both IMRT and protons.

 

[IonsAreOurFuture]

can you explain how proton can possibly be advantageous in pancreatic cancer? are you able to achieve as tight of a fall off adjacent to critical structures like the duodenum as you could with VMAT? In my experience with my friends who have proton, this is always a VMAT case.

We usually can't eliminate overlap of a pancreas head mass with the duodenal C loop, unless a very small primary, in which case it would have had a Whipple already. We can with protons help reduce the entry/ exit dose into the anterior and lateral bowel loops, stomach, transverse colon, liver, kidneys, marrow and spleen.

As with most forms of radiation, the maximum hotspot in an adjoining/overlapping organ will always persist, but the dose to surrounding areas will on average decrease with a proton plan.

The biggest difference of protons compared to IMRT or 3D, in my opinion, is that protons are the only beam we have that actually reduces the integral dose, instead of just moving it from one place to another. The end result is that the integral dose with protons is typically only a third as much as Xrays for similar coverage.

This might matter for immunotherapy and chemotherapy combinations and the GI-006 trial of esophageal cancer will help to determine whether lymphopenia matters.

 

[communitydoc13]

The number one indication for proton therapy in America is breast cancer.

I imagine some women walk in the proton center asking for protons. But I bet many were told by a rad onc protons were best.

In my opinion, every woman asking for protons doesn't need acquiescence, they need education and a refusal to be irradiated via protons.

Wait!!!!

Is that Tim Williams, the former president of ASTRO? HOLY.......

 

[RickyScott]

Astro presidents are almost uniformly bad actors. (With one or 2 exceptions like Brian kavanaugh)

 

[deleted1111261]

Bad actor like Jerry Seinfeld or bad actor like George Santos?

 

[TheWallnerus]

Astro presidents are almost uniformly bad actors. (With one or 2 exceptions like Brian kavanaugh)

Bad actor like Jerry Seinfeld or bad actor like George Santos?

I thought he meant bad actor like Tom Eichler

Through your eyes

Tom Eichler, M’87, H’92, auditioned for the play “Music Man” on a lark. By the end of his first performance, there was no turning back.

medschool.vcu.edu

 

[evilbooyaa]

No offense to Ions or any of the folk here who I genuinely believe to be reasonable professionals, but yesterday I had one of those WTF interactions that reminded me of the unfortunate protoplasm that exists in certain specters of the proton world. Met with a dude who had an in-gland recurrence after prior proton therapy at a center outside of my region a while back. Told me his proton doctor told him that since they used protons and his normal organs were spared, repeat radiation would be no problem (eye roll). When I started talking about risks of any salvage approaches, including bleeding and need for HBO or diversion, he piped up and said "I had to do that oxygen thing last time because of bleeding. My doctor told me if they hadn't used protons, I probably would have needed a bag." (vomit in mouth) I don't care if it's protons, MRaRT, or good ole' fashion IMRT, f****** own up to it when something goes wrong and don't BS your patients.

Man... I don't think my soul could handle working at a proton center treating prostate or breast knowing I was, intentionally or unintentionally, deceiving patients.

We usually can't eliminate overlap of a pancreas head mass with the duodenal C loop, unless a very small primary, in which case it would have had a Whipple already. We can with protons help reduce the entry/ exit dose into the anterior and lateral bowel loops, stomach, transverse colon, liver, kidneys, marrow and spleen.

As with most forms of radiation, the maximum hotspot in an adjoining/overlapping organ will always persist, but the dose to surrounding areas will on average decrease with a proton plan.

The biggest difference of protons compared to IMRT or 3D, in my opinion, is that protons are the only beam we have that actually reduces the integral dose, instead of just moving it from one place to another. The end result is that the integral dose with protons is typically only a third as much as Xrays for similar coverage.

This might matter for immunotherapy and chemotherapy combinations and the GI-006 trial of esophageal cancer will help to determine whether lymphopenia matters.

This is, IMO, moving the goal posts. How does duodenal toxicity be affected by lymphopenia in pancreatic cancer? Like what is the presumed benefit to protons in pancreatic cancer?

In other cancers, let's see about the lymphopenia angle in randomized trials (not retrospective analyses). Protons for NSCLC is a relevant topic - randomized trial negative (protons not good enough?!), now retrospective shows improvement in cytopenias (meh) and ability to receive Durva (potentially relevant) in IMPT patients compared to IMRT. Hypothesis generating.

 

[Chartreuse Wombat]

Man... I don't think my soul could handle working at a proton center treating prostate or breast knowing I was, intentionally or unintentionally, deceiving patients.



This is, IMO, moving the goal posts. How does duodenal toxicity be affected by lymphopenia in pancreatic cancer? Like what is the presumed benefit to protons in pancreatic cancer?

In other cancers, let's see about the lymphopenia angle in randomized trials (not retrospective analyses). Protons for NSCLC is a relevant topic - randomized trial negative (protons not good enough?!), now retrospective shows improvement in cytopenias (meh) and ability to receive Durva (potentially relevant) in IMPT patients compared to IMRT. Hypothesis generating.

It is difficult to get a man to understand something, when his salary depends upon his not understanding it.

Upton Sinclair

 

[drowsy12]

We usually can't eliminate overlap of a pancreas head mass with the duodenal C loop, unless a very small primary, in which case it would have had a Whipple already. We can with protons help reduce the entry/ exit dose into the anterior and lateral bowel loops, stomach, transverse colon, liver, kidneys, marrow and spleen.

As with most forms of radiation, the maximum hotspot in an adjoining/overlapping organ will always persist, but the dose to surrounding areas will on average decrease with a proton plan.

The biggest difference of protons compared to IMRT or 3D, in my opinion, is that protons are the only beam we have that actually reduces the integral dose, instead of just moving it from one place to another. The end result is that the integral dose with protons is typically only a third as much as Xrays for similar coverage.

This might matter for immunotherapy and chemotherapy combinations and the GI-006 trial of esophageal cancer will help to determine whether lymphopenia matters.

Okay so low dose bath and lymphopenia stuff, same as other disease sites. Good luck. I don’t have much optimism.

 

[Doctorer]

Man... I don't think my soul could handle working at a proton center treating prostate or breast knowing I was, intentionally or unintentionally, deceiving patients.



This is, IMO, moving the goal posts. How does duodenal toxicity be affected by lymphopenia in pancreatic cancer? Like what is the presumed benefit to protons in pancreatic cancer?

In other cancers, let's see about the lymphopenia angle in randomized trials (not retrospective analyses). Protons for NSCLC is a relevant topic - randomized trial negative (protons not good enough?!), now retrospective shows improvement in cytopenias (meh) and ability to receive Durva (potentially relevant) in IMPT patients compared to IMRT. Hypothesis generating.

Protons for pancreas is a poor use of resources. The photon plans are better/allow for more confident dose escalation, and you’ve got better imaging.

Reirradiation? Better use.

 

[RickyScott]

Man... I don't think my soul could handle working at a proton center treating prostate or breast knowing I was, intentionally or unintentionally, deceiving patients.



This is, IMO, moving the goal posts. How does duodenal toxicity be affected by lymphopenia in pancreatic cancer? Like what is the presumed benefit to protons in pancreatic cancer?

In other cancers, let's see about the lymphopenia angle in randomized trials (not retrospective analyses). Protons for NSCLC is a relevant topic - randomized trial negative (protons not good enough?!), now retrospective shows improvement in cytopenias (meh) and ability to receive Durva (potentially relevant) in IMPT patients compared to IMRT. Hypothesis generating.

I will be honest and admit I would pimp protons vs move across the country from my family.

 

[IonsAreOurFuture]

I would suggest a slight modification to this:

1. It seems when the GTV directly abuts a critical structure protons alone do not add value and may be deleterious (prostate/pancreas/posterior fossa/central lung/some H&N).
-> Note - PTV under coverage is very reasonable; as @ramsesthenice notes above; w/ Crane/Ablative style panc dosing and OAR PRV prioritization.
2. When the PTV abuts a low Z medium (i.e. chest wall ranging into low-z lung), your integral dose could be worse than a photon plan
3. As such, protons add value only in very specific settings for sparing organs in parallel. They do not add value for sparing organs in series and may actually harm these organs due to RBE uncertainty and lateral penumbra. This contradicts much of the original proton dogma. Q.E.D.



@IonsAreOurFuture - I understand what you are saying; but honestly I am not sure you full understand the what is going on w/ the SOBP and the summation/integral of the downrange dose. If you look at a lot of the physics work from the 2018 (I think?) ASTRO special session on brain stem necrosis; LET and RBE uncertainty, and ways to mitigate it (many of which you address). Your point about a "pure" Bragg peak just does not make sense in regards to the clinical sequalea.

Correct me if I am wrong; but what I imagine happening is similar to how an electron beam creates downrange atomic interactions and builds a fluence/flux of photons that builds up to a asymptotic level over depth.

The crux of the Proton "problem" is that instead of a fluence/flux of photons, it includes a flux of subatomic particles with directionality and energy; and whose RBE is difficult to calculate and/or model; and whose ultimate penetration does not map onto the proton range.

A Bragg peak in the middle of a SOBP mathmatical distribution (i.e. one in the GTV) as you describe; one in which is weighted less than the distal-most Bragg peak; would still possess all the same qualities of the distal Bragg peak (generating the equivilent of subatmoic shotgun blasts of potentially high RBE subatomic buckshot); but with an x% multiplier given the dose at that point is a sum of the different energies. It would still participate in the Asymtotic build-up of flux. We just don't notice that as much since it gets adjusted for in the Proton RBE multiplier and/or it is in the GTV; but it most likely participates in the lateral beam uncertainty/penumbra.

As such; I would propose the "problem" of protons is inseperable from the technology. Unless better mapping/modelling is generated.

Robustness can help but it is an inherent source of error/uncertainty.

Thanks Upgrayedd. You make some really good points, and I think it's probably fair to say that a lot of the original proton dogma was/is wrong and I can still get into warm conversations with my physicists who grew up in the passive scatter era, from which some rules no longer apply.
One concept that I still hear is "use as few beams as possible, because it's faster and the integral dose is lower." Integral dose is usually not that different from an arc plan vs 3D conformal or even APPA; only the high dose vs low dose volumes are different - the main exception being a target that is really close to the skin on one side of the body, where you might use electrons instead of a multi-beam Xray plan or proton plan.

The speed of delivery argument is not so true in a modern pencil beam facility where rotating the gantry is pretty fast and the therapists don't have to go back in the room - in the passive scatter days (still the norm for most proton rooms built circa 2012 and earlier - e.g. Loma Linda, MDACC, MGH, the Procure facilities) - every single beam needs its own: 1. Custom-machined brass aperture block. 2. Range compensator/distal edge shaper, both need to be inserted into the head of the machine like an electron cutout and a custom-printed bolus from dotDecimal. Imagine going in and out of the room 8 times to treat a 7 field IMRT plan. Therapists would get >15 miles worth of steps in per day. VMAT is simply impossible.

More than 2 fields of passive scatter a day = really slow treatment - so some centers, and I was pretty sad to learn this, because it seems kinda stupid, didn't treat every field every day. I'd heard of this being done on Linacs back in the early days of 3D conformal, treating a 4-field pelvis AP-PA one day and opposed laterals the next, so you only need to use 2 sets of custom blocks per day in the pre-MLC era (yes, there was such a time).

The thinking was, "It'll average out into a 4-field box," but we all know that 2.2 Gray per fraction through the whole rectal width every other day is not the same biologically as 1.1 Gray daily.

You are also correct to cite the 2018 workshop on brainstem necrosis as the time that RBE/LET really hit the field hard and people had to look in the mirror and change their ways. One of the things I gleaned from it was that one should simply treat every field every day, and come of the brainstem as much as possible for the boost, and not give more prescribed dose than needed. Just common sensical stuff.

NCI Workshop on Proton Therapy for Children: Considerations Regarding Brainstem Injury - Haas-Kogan 2019 IJROBP - it's a classic paper in proton therapy, free full text online

MGH would treat 2 fields: PA & LPO beam on one day and PA & RPO on the next. One of my physicists once suggested this as being somehow okay and I was pretty upset.

This DVH and plan below from Haas-Kogan, et al, shows a pretty dramatic increase in brainstem dose, going from the assumed fixed RBE = 1.1 to a brainstem RBE = 1.2. Not pretty; you go from 55 Gy max nominal dose to 60 Gy RBE-weighted dose in the brainstem. One recommendation was to not aim more than one beam terminating in the brainstem (usually the PA beam).

Today I can create this type of comparison DVH on Raystation in clinic, and I have already started using it for better beam angle selection. The closer I get to an arc plan (more beams) the less this type of scenario happens, because I don't have all the distal Bragg peaks (the hot pristine ones) ending up in the organ at risk, but rather fanned out all around. LET-based optimization is also in this version of Raystation but I haven't cracked the hood open on that one, yet...

To really learn more about proton LET/RBE and variable RBE, please read AAPM TG-256. It's really quite well done and has about 6 strategies for coping with the problem: https://aapm.onlinelibrary.wiley.com/doi/10.1002/mp.13390 - behind the AAPM paywall but your librarian or physicist can get it for you

To answer your question about, Does the TPS account for dose from secondary particles like scattered electrons, neutrons, etc. Short answer is yes, it's all Monte Carlo based modeling like you would do for an atomic bomb. Raystation is awesome, they even account for induced deuterium and alpha particle formation from rare nuclear interactions; recently learned from a meeting talk I attended. Here's their website. They also talk about 4D motion mgmt for particles, robust CTV-based optimization, LET/RBE, and step-and-shoot proton arcs. Super smart people: Treatment Planning System - RayStation | RaySearch Laboratories One of the few software companies that releases a major upgrade every 6 months.

 

[RickyScott]

How many proton centers are treating with passive scatter and no cbct?

 

[IonsAreOurFuture]

Okay so low dose bath and lymphopenia stuff, same as other disease sites. Good luck. I don’t have much optimism.

I would posit that 20 Gy is no longer considered low dose bath when giving concurrent chemo and XRT to large tumors in the abdomen

 

[IonsAreOurFuture]

How many proton centers are treating with passive scatter and no cbct?

Way too many, IMHO


MDACC built an entirely new 4 room proton center rather than try to upgrade all their old rooms to pencil beam.

The old rooms can do KV/KV pair images but no CBCT at isocenter. Only in their new building.

MGH is shutting down its main proton facility for a total overhaul by IBA. I don't know if it will include CBCTs but it should convert their gantries to pencil beam.

 

[NotMattSpraker]

Way too many, IMHO


MDACC built an entirely new 4 room proton center rather than try to upgrade all their old rooms to pencil beam.

The old rooms can do KV/KV pair images but no CBCT at isocenter. Only in their new building.

MGH is shutting down its main proton facility for a total overhaul by IBA. I don't know if it will include CBCTs but it should convert their gantries to pencil beam.

This kind of stuff makes it a lot easier to understand ASTROs extreme lack of integrity when it comes to protons and payer policy. I get it, it is just sad to see this kind of investment with essentially zero high quality evidence base and the trade off required nationally (ROCR).

I will be honest and admit I would pimp protons vs move across the country from my family.

Me too. At this point I would value taking a job that has no proton center over one that does, all other things equal. So much baggage.

 

[RickyScott]

protons may be an improvement over photons at some point in the future (arc and cbct) but I am convinced the vast majority of proton treatments over the past 15 years are "worse" than vmat photons.

 

[communitydoc13]

at some point in the future (arc and cbct)

It's important that people know that these are not solutions to the intrinsic uncertainty of proton dosimetry.

They will allow for more complicated planning solutions that may be better than what is out there now for adjacent structures. Of course, the more complicated the solution, the more the integral dose advantage of protons will be degraded.

Pencil beam also does not necessarily act as a solution to dosimetric uncertainty. (May even compound it in small volumes).

I am a little concerned about the massive disparities in the literature regarding things like brain necrosis for medulloblastoma in proton patients.
Makes me wonder if the docs are perhaps unintentionally prescribing highly variable doses to these patients?

It is very possible that the toxicity distribution for proton therapy will always be very different (but not necessarily better) than for photons, with a significant portion of patients reaping a small toxicity benefit from reduced integral dose and a small portion of patients suffering from increased higher grade toxicity due to intrinsic dosimetric uncertainty.

e.g. your kid is less likely to have severe growth deficits or second malignancies long term...but this comes with an increased risk of brainstem necrosis and possible locked in syndrome.

Tough stuff and high level stuff.

 

[TheWallnerus]

Kind of a sad state affairs that insurance companies have guidelines that read “protons are considered proven and clinically equivalent to photons for prostate” yet will fight over 6 fractions of LDRT to an arthritic old lady’s knee.