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I know that it is not standard yet , but is anyone doing it ?
ty
ty
If pursuing PCI at all, then in my view, the data is currently stronger for memantine (benefit in RCT) than for HA-WBRT (benefit compared to historical control). So, would at least offer memantine.
Re: PCI: in LS-SCLC, it's still a potentially curative situation, and you're obviously underdosing part of the brain (10%?) in HA-WBRT, so my worry would be that you're compromising the chance of cure. Realistically, though, the only circumstance in which a pt would be harmed is if they had an isolated CNS failure in the underdosed region. Not sure what the rate of isolated CNS failure in LS-SCLC is, but multiply that by the 10% of brain underdosed and it's probably only a few % of pts who would be affected. And even that minority is highly salvageable with SRS. Moreover, if you believe the benefit of HA-WBRT, then most patients probably derive some neurocognitive benefit, which has to be weighed against the few % chance of harm.
So, while I think the proper answer is that HA-PCI should be done only on trial, practically speaking I think it does seem a very attractive proposition.
CC-001 (randomized trial) presented at ASTRO showing benefit of HA-WBRT compared to WBRT even when all patients receive memantine (Hippocampus-Sparing Radiation a New Option in Brain Mets Patients)
Otherwise, agree with rest of your post.
I know that it is not standard yet , but is anyone doing it ?
ty
It is absolutely standard. It's standard like postop chemoRT for gastric became standard after a single study, or definitive chemoRT became standard for OPSCC after a single study, or Tmz became standard after a single study, 8 Gy became standard palliative dose after a single study, etc etc. and ad infinitum.I do it on study; they had closed the NRG study down for interim analysis but it's back open.
I haven't done it off study yet; can people get it approved off study by insurance?
Wonder why this is still "a thing." One, the journal vs. ASTRO abstract review process is not obviously more robust. Two, it has technically been published. Three, odds of non-publication of this are zero. Four, you have knowledge of the outcome: you believe it, or you don't. #contraryAlthough not yet published.
It is absolutely standard. It's standard like postop chemoRT for gastric became standard after a single study, or definitive chemoRT became standard for OPSCC after a single study, or Tmz became standard after a single study, 8 Gy became standard palliative dose after a single study, etc etc. and ad infinitum.
For Medicare patients as you know there is no approval per se; you bill the IMRT, you get paid the IMRT. There are no IMRT site specific limitations... there is simply medical necessity, or there is not. For private insurance: a different ballgame.
Wonder why this is still "a thing." One, the journal vs. ASTRO abstract review process is not obviously more robust. Two, it has technically been published. Three, odds of non-publication of this are zero. Four, you have knowledge of the outcome: you believe it, or you don't. #contrary
As an aside, with non-prophylactic hippocampal sparing WBRT, anyone giving a higher dose to gtv/tumors? I have been asking for 10% to gross disease over 1cm. Seems like you may as well since it is IMRT.
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For Medicare patients as you know there is no approval per se; you bill the IMRT, you get paid the IMRT. There are no IMRT site specific limitations... there is simply medical necessity, or there is not.
That link shows that IMRT is covered for every single cancer ICD10 diagnosis known to man and a few benign conditions too; that said, brain mets are covered on that list. Used to in the "old days" there was a restrictive dx list. Then, there were no codes listed as restrictive. Now I see they're listing every single (cancer) diagnosis code as covered (e.g. LCIS is covered?).Pretty sure Medicare has a list of icd10 codes they will pay imrt for. If it is not on that list you'll get a denial, but there is an appeal process
https://www.google.com/url?sa=t&sou...FjAAegQIAxAB&usg=AOvVaw34ZxOUAS3TE4EfZXoq5Ezo
I'm glad you're pushing. I was being intentionally provocative. I've been involved in the peer review of ASTRO abstracts, JCO, Red Journal, etc. And yes on one hand journal review is more involved (writing out your thoughts/make a nice reviewer writeup etc vs abstract is just a binary decision). On the other hand, the hurdle to full-throated publication is quite less hurdle-some after you've got a late-breaking abstract at ASTRO of phase III trial with a pretty low p-value finding. If anything, I'm telling people who don't see behind the scenes that there's not some secret sauce that goes into journal peer review MUCH more so that abstract peer review. Perhaps what I should say is a researcher should put as much thought, effort, math, science and ethics into an abstract publication as he or she does into a reviewed journal article so that us poor readers can have equal faith in both; I rely on that being true as a reviewer or reader. I like your pub link about abstract/publication discordance for systemic therapies. If I'm reading it right, there's a ~10% really bad discordance rate. If you go 2013-2016, top ~2 abstracts from ASTRO each year (RTOG 9910, RTOG 0841, DART01/05 GICOR, RTOG 0621, COG ACNS0121*, RTOG 0617, Chinese Stage IV esophageal trial, UK Vortex Sarcoma*), 6 studies have been confirmed w/ journal pubs and 2* are unpublished. So. I'm a practice-changer, more often than not, for sockdolager phase III radiation abstracts. AFAIK, I've not had to retreat to old methods because of an abstract flip-flop. When is a standard a standard? When Whelan's 5y data for breast hypofractionation came out in full publication form, everyone I knew at that time said "Nope, not standard." I said it was standard, started offering it. I started offering it when his abstract (for 5y data) appeared! That was *really* controversial.I am going to push back against a few points-
I think it is arguable that peer review for publication is more robust than abstract review for a meeting; I am not saying that either process is without error. I have participated actively in both forms of peer review for more than two decades and peer review for a journal is more involved.
Additionally there is some evidence that the "final product" is discordant from the meeting abstract; occasionally very much so.
I totally mixed my metaphors and forgot that SCLC patients were excluded from CC-001, a "brain mets" trial. (And forgot OP was asking about SCLC PCI.) So it is acceptable to say it's not a standard for SCLC brain mets *or* SCLC PCI for that reason. But for those who want to "extrapolate"... PCI is not prophylactic and is a misnomer. Radiation doesn't prevent malignant seeding of normal tissue; it can only work by treating a malignancy (or maybe causing abscopal effects). So PCI is really treatment of subclinical brain mets and not "prophylactic" any more than whole breast RT post-lumpectomy is prophylactic, postop XRT for anything is not prophylactic etc.1) You may argue that therapeutic HA-WBRT is standard for non-SCLC pts (SCLC was excluded from CC001). HA-PCI for SCLC is pretty clearly not the same thing.
As an aside, with non-prophylactic hippocampal sparing WBRT, anyone giving a higher dose to gtv/tumors? I have been asking for 10% to gross disease over 1cm. Seems like you may as well since it is IMRT.
Sure but I don't think the pci code is in there. Pci isn't the same code as brain metsThat link shows that IMRT is covered for every single cancer ICD10 diagnosis known to man and a few benign conditions too; that said, brain mets are covered on that list. Used to in the "old days" there was a restrictive dx list. Then, there were no codes listed as restrictive. Now I see they're listing every single (cancer) diagnosis code as covered (e.g. LCIS is covered?).
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So, I still don't agree that one should do SIB to gross disease for the reasons I listed above. But if you were going to, I agree that boosting by only 3 Gy seems too little. I don't know what the right number is (not sure anyone really does - grateful for thoughts and the rationale behind them) but more than 3 Gy seems rational. In a sense, this is recapitulating the RTOG 9508 approach without using SRS. Keep in mind that was 37.5 Gy WBRT + 15-24 Gy SRS boost and showed a LC benefit to the treated lesion but not much else (though possibly OS benefit in the best RPA/GPA pts). I think it's unlikely that addition of SIB to HA-WBRT would show more benefit than addition of SRS to conventional WBRT.But why not boost it more than 3 Gy (10%)?
2 cm PTV??2 cm PTV margin
Yes. But why not boost it more than 3 Gy (10%)? Or did I misunderstand? What are you really accomplishing with 33 Gy vs. 30 Gy?
30 Gy with hippocampal avoidance. 10 Gy SIB to gross dz + 2 cm PTV margin. VMAT. Multiple boost targets fine. Would consider boosting any gross dz, not just 1 cm+. Don't see the logic in boosting a 1.3 cm met, but leaving a 0.9 cm and 0.7 cm met alone. Boost all 3 or none at all.
Agree that if you are going to use VMAT, then make the most of it if circumstances make sense (and will probably make sense a lot with sites like lung going forward in terms of going after more durable control).
Not what I'm going to say on boards, but there's a lot of small series out there looking at various SIB-IMRT techniques with whole brain.
So, I still don't agree that one should do SIB to gross disease for the reasons I listed above. But if you were going to, I agree that boosting by only 3 Gy seems too little. I don't know what the right number is (not sure anyone really does - grateful for thoughts and the rationale behind them) but more than 3 Gy seems rational. In a sense, this is recapitulating the RTOG 9508 approach without using SRS. Keep in mind that was 37.5 Gy WBRT + 15-24 Gy SRS boost and showed a LC benefit to the treated lesion but not much else (though possibly OS benefit in the best RPA/GPA pts). I think it's unlikely that addition of SIB to HA-WBRT would show more benefit than addition of SRS to conventional WBRT.
2 cm PTV??
These plans are very hetreogenous and asking for 10% is mainly to obtain 100% coverage of gtvs, and ends up 3-5% and try to force hotspots into gtv with some rings. i guess the question is, should I be asking for more- I dont know. I wouldnt compare it to standard whole brain trials, because usually selecting pts who you hope to have better prognosis and hopefully wont be dead in 4-5 months, which is the average survival in whole brain.
Sorry, typo meant 2 mm. If you're using an SRS mask instead of an IMRT whole brain mask, you could do 1 mm, but no need to do that. I would use the IMRT reinforced mask instead of the standard whole brain mask though.
Agree that the goal here is LC, not OS. And think LC may be more important as control of extracranial disease improves with new molecular agents. Advantage of doing this is it allows you to boost gross disease with no extra treatments like SRS and if you're already doing VMAT anyway for hippocampal sparing, it makes sense (to me at least). Dosimetrist may not like it.
Whole brain doesnt controls most lesions, the patient just dies. 300 x 10 does not eliminate gross disease.
"PCI" only works if there are mets in the brain. (In the pre-PCI era, ~50-70% of patients at death felt to be brain mets-free actually had brain mets at autopsy.) There is no such thing as prophylactic irradiation (well, verbally there is... "in reality" no). So IMHO you have to code brain mets when you do whole brain RT of any sort. Prophylaxis: prevents a disease from occurring. You can't give a pregnancy prophylaxis to a pregnant woman e.g. Else, one is by way of insisting on the whole brain RT being prophylactic that the brain is totally metastasis-free; ergo, insisting on irradiating a completely normal, non-cancerous brain (bad). Am I heretical? Yes. Also, if a trial shows HA-PCI is good for SCLC, Medicare will (likely) not adjust its diagnosis codes to "allow" for IMRT (ie add in the PCI C-code), at least not right away. So what then?Sure but I don't think the pci code is in there. Pci isn't the same code as brain mets
"PCI" only works if there are mets in the brain. (In the pre-PCI era, ~50-70% of patients at death felt to be brain mets-free actually had brain mets at autopsy.) There is no such thing as prophylactic irradiation (well, verbally there is... "in reality" no). So IMHO you have to code brain mets when you do whole brain RT of any sort. Prophylaxis: prevents a disease from occurring. You can't give a pregnancy prophylaxis to a pregnant woman e.g. Else, one is by way of insisting on the whole brain RT being prophylactic that the brain is totally metastasis-free; ergo, insisting on irradiating a completely normal, non-cancerous brain (bad). Am I heretical? Yes. Also, if a trial shows HA-PCI is good for SCLC, Medicare will (likely) not adjust its diagnosis codes to "allow" for IMRT (ie add in the PCI C-code), at least not right away. So what then?
If pursuing PCI at all, then in my view, the data is currently stronger for memantine (benefit in RCT) than for HA-WBRT (benefit compared to historical control). So, would at least offer memantine.
Re: PCI: in LS-SCLC, it's still a potentially curative situation, and you're obviously underdosing part of the brain (10%?) in HA-WBRT, so my worry would be that you're compromising the chance of cure. Realistically, though, the only circumstance in which a pt would be harmed is if they had an isolated CNS failure in the underdosed region. Not sure what the rate of isolated CNS failure in LS-SCLC is, but multiply that by the 10% of brain underdosed and it's probably only a few % of pts who would be affected. And even that minority is highly salvageable with SRS. Moreover, if you believe the benefit of HA-WBRT, then most patients probably derive some neurocognitive benefit, which has to be weighed against the few % chance of harm.
So, while I think the proper answer is that HA-PCI should be done only on trial, practically speaking I think it does seem a very attractive proposition.
Yet we have data documenting an OS benefit for it, and we know the natural history of sclc is a really high intracranial relapse rate long term, but PCI feels strange (not just me right?).
To yield acceptable image quality, the pre-contrast-enhanced should have a resolution of
1 x 1 x 1.2 mm and should follow the protocols established by the Alzheimer’s Disease
Neuroimaging Initiative (ADNI).
I personally think that is unnecessary for hippocampal contouring.
Nice find--thanks.Prior estimates have approximated this risk at 8.6%"
"PCI" only works if there are mets in the brain.
PCI for SCLC is so bizarre and very unsettling to know we are treating people's brain that have no cancer in them and for those that do a very pitiful dose. Yes, I know we do elective treatment volumes and give systemic therapy without knowing, but PCI feels strange (not just me right?).
The very definition of agita. But like Jim Morrison said: people are strange. Heck, to me, the most "prophylactic" of all things we do is give whole breast RT to an older woman with Stage I breast CA post-lumpectomy. We do this for a ~3% absolute local control benefit. In other words, we treat 33 old ladies to help 1. The number needed to treat is not that bad for "prophylactic" cranial irradiation for small cell lung cancer, which also gives a survival benefit. (Again, it is not prophylactic; talk amongst yourselves.)PCI feels strange (not just me right?).
Totally possible.Unless you think PCI is doing something to the brain to inhibit future seeding from systemic sites,
The raison d'etre for our specialty: subclinical disease.I don't think it's controversial that there are likely to be occult tumor cells in the brain below the threshold of detection and that that's what PCI is treating.
Yet we have data documenting an OS benefit for it, and we know the natural history of sclc is a really high intracranial relapse rate long term
Indeed. I've been thinking about the epistemology of clinical trials a lot lately. Expert opinion, retrospective data, and phase II data should not trump phase III trial results, but this happens a lot in oncology. I still give PCI b/c no matter what my hesitations are due to the aforementioned trials.
In the community, it's borderline malpractice imo to not give it esp in LS disease. Still a cat 1 rec by the nccn. I also think it should be given in ES patients with a CR everywhere else
I've had a few patients refuse and I ended up getting called 6-12 mos later to give "T" CI when they had multiple mets
In the community, it's borderline malpractice imo to not give it esp in LS disease. Still a cat 1 rec by the nccn. I also think it should be given in ES patients with a CR everywhere else
I've had a few patients refuse and I ended up getting called 6-12 mos later to give "T" CI when they had multiple mets
While it is a recommended therapy, NCCN also makes allowances for close surveillance with MRI Brain q3 month (assuming that initial pre-treatment MRI is negative) based on the Japanese data.
I agree.Only in ES disease. Limited remains PCI, category 1 no option for surveillance.
Yet we have data documenting an OS benefit for it, and we know the natural history of sclc is a really high intracranial relapse rate long term
Only in ES disease. Limited remains PCI, category 1 no option for surveillance.
This is absolutely correct but with significant caveats. The category 1 recommendation is based on CT era studies without routine CT surveillance for those that did not get PCI.
So the data we have tells us today that if our patient has SCLC and can only have one staging CT head at diagnosis without routine CT surveillance then there is an overall survival advantage to PCI.
The one MRI era study in ES-SCLC was completely negative and shut down early for futility. It was actually trending toward a survival detriment.
Obviously it is still a category 1 recommendation for all LS-SCLC patients. I expect the Japanese to help us end this debate. I think we will look back soon and be embarrassed that we were treating patients without brain metastasis for so long.
Prophylactic is thera... nevermind 25/10How do you guys treat someone who's had complete resolution of 3 small brain mets after completion of chemo and xrt, NED everywhere else, essentially had limited stage disease minus the brain mets which the radiologist hedged on until after the repeat scan was done.
Prophylactic or therapeutic brain dose?
Excellent question.How do you guys treat someone who's had complete resolution of 3 small brain mets after completion of chemo and xrt, NED everywhere else, essentially had limited stage disease minus the brain mets which the radiologist hedged on until after the repeat scan was done.
Prophylactic or therapeutic brain dose?