SpaceOAR - Augmenix, Boston Scientific, and Conflicts of Interest

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What I hate about space oar and protons for that matter is how some proponents traffic in fear. Conventional imrt has very few/negligible side effects but pts often leave these centers with the impression that their rectums will be burned in the community. Snakes eating their tails are not good for the specialty.
 
RickyScott said:
Re proton trial,would love to see if difference in space oar placement between proton and photon groups
Click to expand...

It was the same.

1000005796.jpg
 
Neuronix said:
I don't recall the results being stratified based on spacer usage. Would be an interesting analysis given the controversies.
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From a press release on ASTRO website

IMRT and proton therapy offer equally high quality of life and tumor control for people with prostate cancer - American Society for Radiation Oncology (ASTRO) - American Society for Radiation Oncology (ASTRO)

Press release for research from the 2024 ASTRO Annual Meeting
www.astro.org www.astro.org

"There also were no sustained differences in quality of life or survival between the arms for any pre-defined subgroups: low vs. intermediate risk disease, older vs. younger than 65, yes vs. no rectal spacer use and shortened vs. conventional fractionation schedule."
 
RickyScott said:
With small margins 4/5 mm and modern igrt there is just not a lot of space for toxicty improvement.
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SpaceOAR randomized trial it took a lot of digging (too much) to find their margins, I don’t think it was published in the final article. As I recall they were not 4/5. They were bigger. Someone else will remember or correct me but I’m thinking they were closer to 7.

I think the majority of rad onc is 4 (5 max) posteriorly in standard or hypofrac cases
 
BobbyHeenan said:
SpaceOAR randomized trial it took a lot of digging (too much) to find their margins, I don’t think it was published in the final article. As I recall they were not 4/5. They were bigger. Someone else will remember or correct me but I’m thinking they were closer to 7.

I think the majority of rad onc is 4 (5 max) posteriorly in standard or hypofrac cases
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They allowed 5-10mm margin on the spacer trial, I believe 5-7mm psoteriorly (if not 5-10mm in all directions)
 
MegaVoltagePhoton said:
Just wanted to post this here:

proton trial totally negative

Prostate Advanced Radiation Technologies Investigating Quality of Life (PARTIQoL): Phase III Randomized Clinical Trial of Proton Therapy vs. IMRT for Localized Prostate Cancer​

J.A. Efstathiou1 ∙ B.Y. Yeap2 ∙ J.M. Michalski3∙ … ∙ N.P. Mendenhall11 ∙ E.M. Soffen12 ∙ J.E. Bekelman4… Show more
Affiliations & NotesArticle Info



Abstract​

Purpose/Objective(s)​

Patients with localized prostate cancer have several treatment options including external beam radiotherapy with either photons or protons. Proton beam therapy (PBT) has certain dosimetric advantages with the potential to reduce treatment-associated morbidity and improve oncologic outcomes, but it is generally more resource intensive than intensity modulated radiation therapy (IMRT). To address the hypothesis that PBT results in improved patient-reported outcomes (PROs), PARTIQoL (NCT01617161) was conducted as a multi-center phase 3 randomized trial comparing the two modalities.

Materials/Methods​

Patients with intermediate- or low-risk prostate cancer were randomized to PBT or IMRT, without hormonal therapy, stratified for institution, age, rectal spacer use, and fractionation (79.2 Gy/44 fractions vs 70 Gy/28 fractions). Participants were followed longitudinally to assess PROs of bowel, urinary, and sexual function for 60 months (mo) after completion of radiotherapy. Primary endpoint was to compare change from baseline in bowel quality of life (QOL) using the health care software score (range 0-100) at 24 mo. Secondary objectives include comparison of urinary and sexual functions, toxicity, and efficacy endpoints.

Results​

Between 06/2012-11/2021, 450 patients from 30 recruiting centers were randomized: PBT (N=226) and IMRT (N=224), of whom 221 and 216 were eligible and started radiation on the respective arms. Median follow-up was 60.3 mo among 424 patients still alive. Median age was 68 yrs (range 46-89), 59% had intermediate-risk disease, 51% received hypofractionation, 48% used a rectal spacer, and 49% of PBT patients were treated with pencil beam scanning. There was no difference between PBT or IMRT in mean change of health care software bowel score at 24 mo (p=0.836), with both arms showing only small, clinically non-meaningful decline from baseline (see Table). Similarly, there was no difference in bowel function at earlier timepoints (3, 6, 9, 12, 18 mo) or later timepoints (36, 48, 60 mo). No differences were observed in other domains (urinary, sexual, hormonal) at any timepoint. There was no difference in progression-free survival (PFS) (93.4% vs 93.7% at 60 mo, HR 1.16 [0.53, 2.57], p=0.706). There was no sustained difference in any QOL domain or PFS between arms in subgroups defined by stratification variables.

Conclusion​

This prospective randomized clinical trial shows that patients treated with contemporary radiotherapy for localized prostate cancer achieve excellent QOL with highly effective tumor control, without measurable differences between PBT and IMRT. We continue to monitor participants for longer follow-up and secondary endpoints.

BA 01 – Table 1
Health care software bowel score Mean (Std Dev)PBT (N=221)IMRT (N=216)p-value
Baseline93.7 (7.8)93.5 (7.9)
24 mo91.8 (11.1)91.9 (8.6)
Change-2.4 (9.7)-2.2 (9.1)0.836
Click to expand...

Great, so Medicare and ALL commercial insurances will stop paying for proton therapy for prostate cancer receiving treatment to just the prostate/SVs , now, right? And clearly, proton centers themselves will simply stop treating prostate cancer patients, since there is no advantage to this financially toxic treatment (compared to photon IMRT), right?
Right?

IonsAreOurFuture said:
It's very hard to improve on the cure rate for low and intermediate risk prostate cancer where 95% of patients do well.

It's also difficult to improve on toxicity of IMRT+IGRT to prostate alone using narrow margins, where 95% of patients do well.

This may come as something of an existential threat to some proton centers, as the average case load is about 25% prostates nationwide. There is very little difference between the dosimetry of a proton and IMRT plan for prostate-only treatment.

I personally think that high risk and very high risk disease is a different story, or when treating gross positive nodes, because there is a noticeable difference in bowel, bladder and sigmoid sparing when treating whole pelvis. Such a proton vs IMRT trial (high risk, +nodes) has yet to launch, but I would be happy to enroll on it.
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For gross nodes needing a boost - maybe, just maybe. Would be interested in a trial
For just ENI, doubt it.
However, not unreasonable to re-run this trial in high-risk patients receiving ENI.

If you're at a proton center who sees a FIR patient who wants radiation, you sending them away to go get cheaper photon IMRT?
 
MegaVoltagePhoton said:
Just wanted to post this here:

proton trial totally negative

Prostate Advanced Radiation Technologies Investigating Quality of Life (PARTIQoL): Phase III Randomized Clinical Trial of Proton Therapy vs. IMRT for Localized Prostate Cancer​

J.A. Efstathiou1 ∙ B.Y. Yeap2 ∙ J.M. Michalski3∙ … ∙ N.P. Mendenhall11 ∙ E.M. Soffen12 ∙ J.E. Bekelman4… Show more
Affiliations & NotesArticle Info



Abstract​

Purpose/Objective(s)​

Patients with localized prostate cancer have several treatment options including external beam radiotherapy with either photons or protons. Proton beam therapy (PBT) has certain dosimetric advantages with the potential to reduce treatment-associated morbidity and improve oncologic outcomes, but it is generally more resource intensive than intensity modulated radiation therapy (IMRT). To address the hypothesis that PBT results in improved patient-reported outcomes (PROs), PARTIQoL (NCT01617161) was conducted as a multi-center phase 3 randomized trial comparing the two modalities.

Materials/Methods​

Patients with intermediate- or low-risk prostate cancer were randomized to PBT or IMRT, without hormonal therapy, stratified for institution, age, rectal spacer use, and fractionation (79.2 Gy/44 fractions vs 70 Gy/28 fractions). Participants were followed longitudinally to assess PROs of bowel, urinary, and sexual function for 60 months (mo) after completion of radiotherapy. Primary endpoint was to compare change from baseline in bowel quality of life (QOL) using the health care software score (range 0-100) at 24 mo. Secondary objectives include comparison of urinary and sexual functions, toxicity, and efficacy endpoints.

Results​

Between 06/2012-11/2021, 450 patients from 30 recruiting centers were randomized: PBT (N=226) and IMRT (N=224), of whom 221 and 216 were eligible and started radiation on the respective arms. Median follow-up was 60.3 mo among 424 patients still alive. Median age was 68 yrs (range 46-89), 59% had intermediate-risk disease, 51% received hypofractionation, 48% used a rectal spacer, and 49% of PBT patients were treated with pencil beam scanning. There was no difference between PBT or IMRT in mean change of health care software bowel score at 24 mo (p=0.836), with both arms showing only small, clinically non-meaningful decline from baseline (see Table). Similarly, there was no difference in bowel function at earlier timepoints (3, 6, 9, 12, 18 mo) or later timepoints (36, 48, 60 mo). No differences were observed in other domains (urinary, sexual, hormonal) at any timepoint. There was no difference in progression-free survival (PFS) (93.4% vs 93.7% at 60 mo, HR 1.16 [0.53, 2.57], p=0.706). There was no sustained difference in any QOL domain or PFS between arms in subgroups defined by stratification variables.

Conclusion​

This prospective randomized clinical trial shows that patients treated with contemporary radiotherapy for localized prostate cancer achieve excellent QOL with highly effective tumor control, without measurable differences between PBT and IMRT. We continue to monitor participants for longer follow-up and secondary endpoints.

BA 01 – Table 1
Health care software bowel score Mean (Std Dev)PBT (N=221)IMRT (N=216)p-value
Baseline93.7 (7.8)93.5 (7.9)
24 mo91.8 (11.1)91.9 (8.6)
Change-2.4 (9.7)-2.2 (9.1)0.836
Click to expand...
Feel like this needs to be split off into its own thread, esp with some possible shenanigans happening over at mednet:

@evilbooyaa @Neuronix

"As PARTIQOL was a negative study, what is the current role for proton therapy in the management of prostate cancer patients?"

That question was about the role of protons in prostate cancer after partiqol results. It was answered and then deleted on mednet it seems

Krishnan Patel had an excellent and comprehensive answer

Simul then basically posted saying its negative, there's a lot advertisements and they are promising higher cures and lower tox. And that Astro is saying "2 great choices" while browbeating us with fractionation and imrt.

Anyone know how to use a wayback machine to see that it was there before?

I reached out to Simul and he forwarded me a letter he sent out to mednet regarding this:

Dear TheMedNet Editorial Team,

I am writing to express my deep concern about the removal of my recent post discussing proton therapy for prostate cancer, along with Dr. Krishnan Patel's thoughtful response. The topic of proton therapy, especially in light of recent findings from the PARTIQoL trial, deserves open and honest debate among clinicians, and I was dismayed to see this opportunity for discourse censored.

Prostate cancer, being one of the most commonly treated malignancies, often involves difficult decisions around therapy, particularly when it comes to highly expensive technologies like proton beam therapy. The PARTIQoL study, which compared proton therapy to intensity-modulated radiation therapy (IMRT), provided us with important data showing no significant differences in tumor control or quality of life between the two modalities. This randomized, multicenter trial, involving nearly 450 patients, demonstrated that IMRT and proton therapy are similarly effective, yet proton therapy comes with a much higher cost

While proton therapy certainly has a role in treating specific cancers—such as pediatric cases, where minimizing radiation exposure to surrounding tissue is paramount—its routine use for prostate cancer is questionable. The excessive promotion of protons through various channels (advertising, cancer centers, and media) without sufficient emphasis on clinical evidence is troubling.

The PARTIQoL study’s findings underscore the importance of critical evaluation in our practice, rather than being swayed by marketing or industry influence.

TheMedNet serves as a valuable forum for experts to discuss and debate these complex issues, and it is disheartening to see censorship of a topic that demands attention.
Clinicians should feel free to challenge practices that, while heavily promoted, may not offer substantial clinical benefit, especially when they impose significant financial burdens on healthcare systems and patients.

The proton therapy industry is indeed influential, but it is crucial that as medical professionals, we prioritize evidence-based medicine over industry-driven agendas. The removal of my post gives the impression that even platforms like TheMedNet are hesitant to allow critical discussions when they challenge entrenched industry interests. I believe that fostering such discussions is in the best interest of patient care and scientific integrity.

I respectfully urge you to reconsider the decision to remove the post and to promote a balanced, evidence-based discourse on this critical issue. The conversation around proton therapy for prostate cancer is far from over, and TheMedNet has an important role to play in advancing it.


Sincerely,

Simul Parikh, M.D.
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I would just like to remind everyone this is consistent with what Nancy Lee said in 2019. Big Rad Onc does NOT care about EBM as it relates to protons. Never have, likely never will, but you damn well better hypo-fractionationate your photon cases, little rad onc!

x.com

x.com x.com
 
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medgator said:
Feel like this needs to be split off into it's own thread esp with some possible shenanigans happening over at mednet

@evilbooyaa @Neuronix

"As PARTIQOL was a negative study, what is the current role for proton therapy in the management of prostate cancer patients?"

That question was about the role of protons in prostate cancer after partiqol results. It was answered and then deleted on mednet it seems

Krishnan Patel had an excellent and comprehensive answer

Simul then basically posted saying its negative, there's a lot advertisements and they are promising higher cures and lower tox. And that Astro is saying "2 great choices" while browbeating us with fractionation and imrt.

Anyone know how to use a wayback machine to see that it was there before?

I reached out to Simul and he forwarded me a letter he sent out to mednet regarding this:


I would just like to remind everyone this is consistent with what Nancy Lee said in 2019. Big Rad Onc does NOT care about EBM as it relates to protons. Never have, likely never will, but you damn well better hypo-fractionationate your photon cases, little rad onc!

x.com

x.com x.com
Click to expand...
How do we know protons are better for kids vs imrt. Yes, imrt has low dose bath, but protons also have high let effects in the spread out Bragg peak
 
radoncftw said:
probably saw that it was out there (here on SDN...) that they censored.
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Still not discoverable from main mednet page from what I can tell via author search

It's fishy whatever it is and definitely makes me lose a little respect for MN. I'd expect this nonsense from ASTRO ROHub
 
What is ASTRO’s nature?

They cure cancers and help people?
1728658400441.png


They are only interested in their personal enrichment, self-aggrandizement, and being right even when their own data is to the contrary?

Correct, now please donate to ASTRO PAC.
 
medgator said:
Still not discoverable from main mednet page from what I can tell via author search

It's fishy whatever it is and definitely makes me lose a little respect for MN. I'd expect this nonsense from ASTRO ROHub
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thats true. i think i googled it and found it
 
RickyScott said:
How do we know protons are better for kids vs imrt. Yes, imrt has low dose bath, but protons also have high let effects in the spread out Bragg peak
Click to expand...
We don't know, but I am willing to hedge in some circumstances.

IMO the risk of protons lies in local dose uncertainties that can result in significant focal underdosing/overdosing. Also, as protons slow, they become chemical entities, so lots of underlying uncertainty there as well.

Still, even if giving 18 Gy CSI to a young child, the long term sequelae in terms of growth/development/cognition and second malignancy just suck so bad with photons.

Proton Radiotherapy for Management of Medulloblastoma: A Systematic Review of Clinical Outcomes - PMC

The aim of this study was to comprehensively review all studies examining clinical outcomes of craniospinal irradiation with proton radiotherapy for medulloblastoma (MB) to determine whether theoretical dosimetric advantages have translated into ...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Not great data, but something. Also...I have never seen good reporting of rare severe toxicity (it's not a trivial amount).

If I had a 3 year old with medullo...I'd get protons (based on what's out there now).
 
evilbooyaa said:
Great, so Medicare and ALL commercial insurances will stop paying for proton therapy for prostate cancer receiving treatment to just the prostate/SVs , now, right? And clearly, proton centers themselves will simply stop treating prostate cancer patients, since there is no advantage to this financially toxic treatment (compared to photon IMRT), right?
Right?


For gross nodes needing a boost - maybe, just maybe. Would be interested in a trial
For just ENI, doubt it.
However, not unreasonable to re-run this trial in high-risk patients receiving ENI.

If you're at a proton center who sees a FIR patient who wants radiation, you sending them away to go get cheaper photon IMRT?
Click to expand...
I'm lucky to have access to good linacs and good protons. I'm pretty selective and talked a guy out of protons this week who came in requesting it for Int. Risk dz. I let him know about PARTIQOL and it seemed to calm him down. Some of my proton physicists are another matter and remain convinced protons are somehow inherently better despite randomized trial results.

In my opinion, unless there's a major dosimetric advantage, there won't and can't be any clinical advantage, (unless maybe boosting with LET/RBE), and there is often less dosimetric advantage when treating a whole organ in the midline. It's a little like treating a whole brain with protons - what are you sparing compared to Xrays?

The smart way to use protons is to take advantage of their stopping power and lack of exit dose. Treating pelvic nodes while staying out of the midline makes a lot of sense to me and really does cut the rectal, bladder, sigmoid and small bowel loop dose.

Especially for gross nodes 1 cm in size; if that node were a nodule in the prostate I'd be trying to microboost it FLAME style to over 90 Gy right? Oops, but not next to the small bowel, though with protons I am able to get 70+ Gy in usually and still stop short of the bowel wall.

I think we need COMPPARE 2.0 to be a whole pelvis trial for high/very high risk and another arm for boosting gross nodes.

I don't have much hope for a prostate-only future in proton therapy, except maybe for reirradiation of in-gland-only failures as an alternative to brachy.
 
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communitydoc13 said:
We don't know, but I am willing to hedge in some circumstances.

IMO the risk of protons lies in local dose uncertainties that can result in significant focal underdosing/overdosing. Also, as protons slow, they become chemical entities, so lots of underlying uncertainty there as well.

Still, even if giving 18 Gy CSI to a young child, the long term sequelae in terms of growth/development/cognition and second malignancy just suck so bad with photons.

Proton Radiotherapy for Management of Medulloblastoma: A Systematic Review of Clinical Outcomes - PMC

The aim of this study was to comprehensively review all studies examining clinical outcomes of craniospinal irradiation with proton radiotherapy for medulloblastoma (MB) to determine whether theoretical dosimetric advantages have translated into ...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

Not great data, but something. Also...I have never seen good reporting of rare severe toxicity (it's not a trivial amount).

If I had a 3 year old with medullo...I'd get protons (based on what's out there now).
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I like that medulloblastoma report. I honestly thought the comparison would have been negative. After so much whole brain dose with CSI, what is there left to spare? Hippocampus still cares about additional dose above 20 Gy, I guess, which sort of surprised me.

The big irony of the study is that it was done by Canadian researchers who will still lack access to proton therapy for the next 5 years, sadly. I guess their payors are hard to convince too.

The interesting thing is, had Canada built a center 8 years ago, it would have paid for itself by now in what $$ the government and patients have been sending out of country for treatments at MGH, UPENN and Florida, etc. and avoided the big run up in Toronto real estate, inflation, and interest rates to pay for it.
 
IonsAreOurFuture said:
I like that medulloblastoma report. I honestly thought the comparison would have been negative. After so much whole brain dose with CSI, what is there left to spare? Hippocampus still cares about additional dose above 20 Gy, I guess, which sort of surprised me.

The big irony of the study is that it was done by Canadian researchers who will still lack access to proton therapy for the next 5 years, sadly. I guess their payors are hard to convince too.

The interesting thing is, had Canada built a center 8 years ago, it would have paid for itself by now in what $$ the government and patients have been sending out of country for treatments at MGH, UPENN and Florida, etc. and avoided the big run up in Toronto real estate, inflation, and interest rates to pay for it.
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I would not call the report strong data, but the priors regarding some outcomes are so high that I will roll with it for this particular situation. (However, I am concerned about risks of brainstem necrosis with protons...I do not believe this is adequately reported, and I am aware from personal communications that this does happen).

One would fully expect protons to spare thyroid and gonads preferentially to photons. These are also exquisitely radiosensitive organs. Protons can likely be employed to spare the pituitary as well. They should spare bony spine.

The endocrine axis alone may explain the observed differential in all outcomes mentioned, including cognition. It may have nothing to do with the hippocampus (I think it probably doesn't).

I am also advocating for protons here because the prescribed dose is so low (as is typical for many peds indications). This reduces the risk of some of the inherent uncertainties associated with protons.

PEDs solid cancers are remarkably rare ~500 medulloblastomas and Wilms per year. It does not take many centers nationally to manage this type of load. I have no problem with 8 regional proton centers affiliated with academic centers and pediatric hospitals.

Peds allows for different thinking. Treating every pediatric CA and congenital heart disease is not going to be associated with significant changes in population health, but it is a great human victory and should be pursued. The bean counters should consider this...but, this is also not the narrative or motivation that has driven proton expansion...at all. I would advocate for protons as a judicious loss leader...kind of like peds is for hospitals overall.

IonsAreOurFuture said:
Especially for gross nodes 1 cm in size; if that node were a nodule in the prostate I'd be trying to microboost it FLAME style to over 90 Gy right? Oops, but not next to the small bowel, though with protons I am able to get 70+ Gy in usually and still stop short of the bowel wall.
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Sounds dicey to me. You don't really know what the dose is in close proximity to your target. Bowel often abuts the pelvic side wall and most severe late bowel toxicity is associated with low volume/high dose situations and not larger volume low dose bath. If there is a proton trial that has a statistically insignificant but raw increase in grade 4 bowel toxicity and some improvement in grade 2 bowel toxicity, I'm calling BS.., analogous to the SpaceOAR situation.
 
RickyScott said:
How do we know protons are better for kids vs imrt. Yes, imrt has low dose bath, but protons also have high let effects in the spread out Bragg peak
Click to expand...

Interestingly, the last pediatric patient that I sent to a proton center (with medullo), ended up getting photons. I read the consult note and it said they offered the 2 options and explained there was a higher rate of radionecrosis with protons, so he selected photons.
 
thesauce said:
Interestingly, the last pediatric patient that I sent to a proton center (with medullo), ended up getting photons. I read the consult note and it said they offered the 2 options and explained there was a higher rate of radionecrosis with protons, so he selected photons.
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Was that recent or awhile ago?

If it was a while ago I hope that hasn’t stopped you from sending pediatric patients out afterwards
 
drowsy12 said:
Was that recent or awhile ago?

If it was a while ago I hope that hasn’t stopped you from sending pediatric patients out afterwards
Click to expand...

It was about 1 year ago. I still send - if anything it reinforced my decision to do so. It was nice to see the thought put into it rather than automatic protons.
 
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I had a patient with prostate cancer visit a very large, very well-known medical center this past week after ASTRO.

They were, naturally, offered proton therapy for their prostate cancer and will be starting treatment soon.
 
OTN said:
I had a patient with prostate cancer visit a very large, very well-known medical center this past week after ASTRO.

They were, naturally, offered proton therapy for their prostate cancer and will be starting treatment soon.
Click to expand...
EBM EFM! (Evidence-free medicine)
 
IonsAreOurFuture said:
I'm lucky to have access to good linacs and good protons. I'm pretty selective and talked a guy out of protons this week who came in requesting it for Int. Risk dz. I let him know about PARTIQOL and it seemed to calm him down. Some of my proton physicists are another matter and remain convinced protons are somehow inherently better despite randomized trial results.

In my opinion, unless there's a major dosimetric advantage, there won't and can't be any clinical advantage, (unless maybe boosting with LET/RBE), and there is often less dosimetric advantage when treating a whole organ in the midline. It's a little like treating a whole brain with protons - what are you sparing compared to Xrays?

The smart way to use protons is to take advantage of their stopping power and lack of exit dose. Treating pelvic nodes while staying out of the midline makes a lot of sense to me and really does cut the rectal, bladder, sigmoid and small bowel loop dose.

Especially for gross nodes 1 cm in size; if that node were a nodule in the prostate I'd be trying to microboost it FLAME style to over 90 Gy right? Oops, but not next to the small bowel, though with protons I am able to get 70+ Gy in usually and still stop short of the bowel wall.

I think we need COMPPARE 2.0 to be a whole pelvis trial for high/very high risk and another arm for boosting gross nodes.

I don't have much hope for a prostate-only future in proton therapy, except maybe for reirradiation of in-gland-only failures as an alternative to brachy.
Click to expand...

How confident are you that what you are seeing on the computer screen is what the patient is getting? Due to variable RBE the discrepancy between what the computer screen shows and what the patient gets can vary by upwards of 50%. Which is why some of the worst 'high-dose' toxicities are always from proton papers that 'seemingly' didn't prescribe doses of radiation that would cause that.
 
evilbooyaa said:
How confident are you that what you are seeing on the computer screen is what the patient is getting? Due to variable RBE the discrepancy between what the computer screen shows and what the patient gets can vary by upwards of 50%. Which is why some of the worst 'high-dose' toxicities are always from proton papers that 'seemingly' didn't prescribe doses of radiation that would cause that.
Click to expand...

Why do people believe that we are just like 10 Gy away from a cure across all settings in cancer care?

Lots of LTE and RBE talk but remember many proton centers until recently were back to first gen OBI with less reliable set ups too.

In my last job if I did proton lung SBRT, I got kV kV and thats it. If I did photon lung SBRT I got CBCT and orthogonal kV fluoro with triggered imaging. I hated proton lung SBRT.
 
NotMattSpraker said:
Why do people believe that we are just like 10 Gy away from a cure across all settings in cancer care?

Lots of LTE and RBE talk but remember many proton centers until recently were back to first gen OBI with less reliable set ups too.

In my last job if I did proton lung SBRT, I got kV kV and thats it. If I did photon lung SBRT I got CBCT and orthogonal kV fluoro with triggered imaging. I hated proton lung SBRT.
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Not sure if the bolded is meant for me - 10Gy is generally not the difference in cancer cure but can certainly be the difference in significant high-grade toxicity especially if you aren't even thinking about it
 
evilbooyaa said:
Not sure if the bolded is meant for me - 10Gy is generally not the difference in cancer cure but can certainly be the difference in significant high-grade toxicity especially if you aren't even thinking about it
Click to expand...

Not meant for anyone in particular.

Also realize that dose escalation did have a lot of benefit in our history.
 
evilbooyaa said:
Not sure if the bolded is meant for me - 10Gy is generally not the difference in cancer cure but can certainly be the difference in significant high-grade toxicity especially if you aren't even thinking about it
Click to expand...

I actually might argue that 10 Gy higher in most cancers probably would be a cure. Obviously, you gotta keep the toxicity down to get there.
 
thesauce said:
I actually might argue that 10 Gy higher in most cancers probably would be a cure. Obviously, you gotta keep the toxicity down to get there.
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10Gy+ more in NSCLC and esophagus and GBM have been studies, and are specifically not curative. Anal probably not given we dose de-escalated from 59.4 to 54 already without issue. HPV H&N we know dropping dose by 10Gy from 70 --> 60 lead to less cures but idk if we have evidence that 80Gy would cure more patients, even in H&N-. Certainly would be feasible to do in the IMRT era...

So in temrs of 10Gy more adding to cure - Cervix yes, for sure (compared to say 80 or 85). Not sure that we have data in any other disease site.
 
evilbooyaa said:
10Gy+ more in NSCLC and esophagus and GBM have been studies, and are specifically not curative. Anal probably not given we dose de-escalated from 59.4 to 54 already without issue. HPV H&N we know dropping dose by 10Gy from 70 --> 60 lead to less cures but idk if we have evidence that 80Gy would cure more patients, even in H&N-. Certainly would be feasible to do in the IMRT era...

So in temrs of 10Gy more adding to cure - Cervix yes, for sure (compared to say 80 or 85). Not sure that we have data in any other disease site.
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"The slope of the dose-response curve, or increment in control per unit increase in dose, reaches a maximum at the 37% (model 2) or 50% (model 3) level, after which it decreases with increasing dose. Consequently, the dose required for a given increase in control is greater at higher
control rates...These results indicate that, at the dose levels presently employed at M. D. Anderson Hospital, increases in dose necessary
to produce further significant increases in local control are likely to be fraught with unacceptable increases in the complication rate."

It's a good read, I recommend it
 
evilbooyaa said:
10Gy+ more in NSCLC and esophagus and GBM have been studies, and are specifically not curative. Anal probably not given we dose de-escalated from 59.4 to 54 already without issue. HPV H&N we know dropping dose by 10Gy from 70 --> 60 lead to less cures but idk if we have evidence that 80Gy would cure more patients, even in H&N-. Certainly would be feasible to do in the IMRT era...

So in temrs of 10Gy more adding to cure - Cervix yes, for sure (compared to say 80 or 85). Not sure that we have data in any other disease site.
Click to expand...

Right, I was talking 10 Gy from today's standard. Because we are living in and treating patients today 🙂

Of course I agree dose escalation helped us in NSCLC. We have not been able to show in a phase III trial that it is helpful beyond today's standard.

Im also not saying it will never be helpful in the future. I am implying people need to come up with new ideas, especially if your idea is to re-run a previously completed dose escalation trial... but with protons.
 
pikachu said:
"The slope of the dose-response curve, or increment in control per unit increase in dose, reaches a maximum at the 37% (model 2) or 50% (model 3) level, after which it decreases with increasing dose. Consequently, the dose required for a given increase in control is greater at higher
control rates...These results indicate that, at the dose levels presently employed at M. D. Anderson Hospital, increases in dose necessary
to produce further significant increases in local control are likely to be fraught with unacceptable increases in the complication rate."

It's a good read, I recommend it
Click to expand...

Are we seriously considering feasibility of dose escalation based on a paper from 1980??

NotMattSpraker said:
Right, I was talking 10 Gy from today's standard. Because we are living in and treating patients today 🙂

Of course I agree dose escalation helped us in NSCLC. We have not been able to show in a phase III trial that it is helpful beyond today's standard.

Im also not saying it will never be helpful in the future. I am implying people need to come up with new ideas, especially if your idea is to re-run a previously completed dose escalation trial... but with protons.
Click to expand...

Fair - I do think pancreas going from 50.4/28 to BED100 (50/5, 67.5/15, 75/25) will hopefully show some benefit as well.
 
evilbooyaa said:
Are we seriously considering feasibility of dose escalation based on a paper from 1980??



Fair - I do think pancreas going from 50.4/28 to BED100 (50/5, 67.5/15, 75/25) will hopefully show some benefit as well.
Click to expand...
Do you think properties of cellular response to radiation have changed since then?
 
pikachu said:
Do you think properties of cellular response to radiation have changed since then?
Click to expand...
Them fits though 😂. Any negative exponential is gonna look kinda like this. Must have been great to be a physician scientist in those days....come up with a plausible model....eff the error bars (they are kinda b.s. anyway in most basic translational stuff)...and impact SOC for decades to come.

What's crazy is that these are roughly the doses we use today! 70 Gy works pretty good for bigger stuff...mid 60s OK for smaller stuff...moving the needle past 80-90% LC is very hard and the variable mechanisms for even local failure mean you are never going to approach unity. They figured this ish out in the 60s!

It's almost like we are only a bit better than clinical dosimetry!

The best ways to increase LC for many tumors? Shorten treatment time and add chemo or other systemic therapy.
 
communitydoc13 said:
Them fits though 😂. Any negative exponential is gonna look kinda like this. Must have been great to be a physician scientist in those days....come up with a plausible model....eff the error bars (they are kinda b.s. anyway in most basic translational stuff)...and impact SOC for decades to come.

What's crazy is that these are roughly the doses we use today! 70 Gy works pretty good for bigger stuff...mid 60s OK for smaller stuff...moving the needle past 80-90% LC is very hard and the variable mechanisms for even local failure mean you are never going to approach unity. They figured this ish out in the 60s!

It's almost like we are only a bit better than clinical dosimetry!

The best ways to increase LC for many tumors? Shorten treatment time and add chemo or other systemic therapy.
Click to expand...
Not to mention that it makes perfect sense for the curve to flatten at higher doses over a fractionated course… since presumably you’re killing off sensitive clones and selecting for more radioresistant cells…
 
pikachu said:
Do you think properties of cellular response to radiation have changed since then?
Click to expand...

I believe there is a separate model of cell kill that happens with high dose per fx treatments than just the linear quadratic formula version we use for conventional fractionation.

I suppose specifically for things in GI mucosa (as per the paper you linked), sure may be difficult. But for 95% of the rest of Rad Onc, we can deliver much more dose to an area while keeping treatments with minimal to tolerable toxicity thanw e ever could in 1980.
 
communitydoc13 said:
Them fits though 😂. Any negative exponential is gonna look kinda like this. Must have been great to be a physician scientist in those days....come up with a plausible model....eff the error bars (they are kinda b.s. anyway in most basic translational stuff)...and impact SOC for decades to come.

What's crazy is that these are roughly the doses we use today! 70 Gy works pretty good for bigger stuff...mid 60s OK for smaller stuff...moving the needle past 80-90% LC is very hard and the variable mechanisms for even local failure mean you are never going to approach unity. They figured this ish out in the 60s!

It's almost like we are only a bit better than clinical dosimetry!

The best ways to increase LC for many tumors? Shorten treatment time and add chemo or other systemic therapy.
Click to expand...

Or we could explore hyperfractionation, which has shown more promise than hypofractionation. However, I'm sure we won't due to the cost.
 
communitydoc13 said:
Them fits though . Any negative exponential is gonna look kinda like this. Must have been great to be a physician scientist in those days....come up with a plausible model....eff the error bars (they are kinda b.s. anyway in most basic translational stuff)...and impact SOC for decades to come.

What's crazy is that these are roughly the doses we use today! 70 Gy works pretty good for bigger stuff...mid 60s OK for smaller stuff...moving the needle past 80-90% LC is very hard and the variable mechanisms for even local failure mean you are never going to approach unity. They figured this ish out in the 60s!

It's almost like we are only a bit better than clinical dosimetry!

The best ways to increase LC for many tumors? Shorten treatment time and add chemo or other systemic therapy.
Click to expand...
It's amazing to me that 45 Gy BID in small cell lung has yet to be beat.
 
IonsAreOurFuture said:
Awesome, thank you for correcting me!

I had meant that no once daily regimen eg 60 gy or 66 gy in 2 gy fractions was better than BID 45, but I can now go to 60 BID and improve OS.
Click to expand...

I've been doing this on patients where I can achieve tradiational 45 Gy goals and constraints, and it has been going well. This certainly deserves a phase III, hopefully it comes at some point.
 
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