United Health Care - Bone Met
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Systemic therapy has changed since 2010… quite a bit. I have oligoprogressive SCLC patients in whom I am playing wack-a-mole 2.5 years out.
When someone with initially widely metastatic cancer has one site of progression on IO/targeted therapy… it’s hard to imagine NOT treating it definitively. Furthermore, a trial in this space is feeling increasingly preposterous…
Like doing an RCT to see if bandages improve outcomes in wounded patients.
What do you mean lack of studies? Like I don’t understand what this means.
There are nearly ten trials that have been presented or published thus far and counting
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What’s the control arm… watching the mass grow?
so there has been one trial in the oligoprogressive space. the CURB trial. included two histologies. there was a benefit for NSCLC, and none at all for breast.
you really arent willing to believe that all of the hype you have fed yourself may not be true? you used the word 'preposterous'. come on.
BR002 stone cold negative as well.
maybe....just maybe..... histology matters (and past histology biology, but we aren't there yet) and we should at least run the trials before you declare 'Mission Accomplished'
I treat oligoprogressors too but I don't ever for a second assume it's a done deal and im definitely helping someone.
when rad onc starts to believe their own farts smell amazing is why we have so many problems.
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Is it?
I mean I would just like to really, really know if all the new systemic treatments of which you speak have changed the natural history of these diseases that local radiation therapy now functions as a survival prolonger in metastatic disease. It’s been tough to prove that radiation is a survival prolonger in many locoregional disease settings. Are we playing whack a mole due to the systemics allowing us to do so, the radiation allowing to do so, or with a wave of hands say “it is a complex interplay.” Sorry. I’m just a die hard skeptic. I do the SBRT and the whack a mole 100% of the time… at med onc’s behest.
The systemic therapy is changing almost monthly now. The radiation never changes. The radiation will always just improve OS no matter what? Should it be constantly continuously tested as the systemics change?
agree.
To paraphrase my reductionist question to JD…
Patient with metastatic something on TKI or IO with solitary growing mass in lung, liver, adrenal etc. What do you do… treat it or watch it?
RT is like surgery… it’s physical, not biological. Biology can either cooperate or not, but RT will usually shrink down a growing mass, even when the 6-figure new drug fails.
Not sure where you think the money to run these trials are coming from. They ain't free. For example, at the low end of ~3k/accrual (the going rate for many cooperative group trials), losing money paying for the coordinators, regulatory, etc to support the trial.
Academic institutions on the whole are milking almost all the money out of a radiation oncology department to subsidize other departments. Good luck squeezing any back to support radiation research. The CEO/Dean/Whoever has a a high likelihood of hating and/or disrespecting radiation.
Device manufacturers aren't paying for these trials, at least historically. This has been changing, but only in the last few years, and that pot of money is a drop in the bucket compared to drug pharma.
Only one cooperative group cares much about radiation, so I guess you can blame them for not running trials. But co-operative groups are like any other consensus body, avoiding risk (ie "out of the box" trials like oligomets and oligoprogressive -- seen trial concepts in both spaces torn to pieces 5-7 years ago or so) and supporting easy "wins" that accrue.
It’s straight up grift to sbrt most mets outside oligoprogressive setting. 5+ years ago ko mentioned on mednet that Mayo was recouping 60-80k for sbrt bone Mets.
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deleted1111261
This is probably true.
But it doesn’t change the fact as a RadOnc that it’s disappointing the data doesn’t exist so we are fighting with Evicore and HealthHelp asking for a few fractions that the damn reviewer themselves would want if they were sick.
Ok so you can shrink an oligoprogressive mass. Make it disappear even. Outside of nsclc, what meaningful endpoint is this going to improve and what evidence is there to support that?
Even CURB - history is rife with trials showing a PFS benefit that did not translate to OS. In “new” era of oligomets, IO, targeted agents, advanced imaging, what does PFS mean? It’s not validated as a surrogate endpoint. Sabr-comet is a start but can we really hang our hat on that and apply to all histologies, systemic therapies, and variation of presentation (oligomet vs oligoprogression)
Post-protocol therapy is a huge huge confounding factor and haven’t seen any info for this on any of the oligomet trials. The systemic therapy is so so important and I have my suspicions about it for some of these studies as it’s not reported
IMO rad oncs have jumped the gun and lost equipoise on this prematurely. It’s unfortunate because may result in less enthusiasm for definitive ph3 trials powered for OS, which is an attitude espoused in this thread.
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A solitary asymptomatic mass in the liver in a breast cancer patient eg? What is the “EBM” answer…
At presentation vs growing through systemic therapy? Good systemic options remaining?
If it’s growing and there isn’t much left to try from a systemic therapy standpoint, would SBRT or resect… not sure there is evidence either way for this
There is some nuance between oligometastatic and oligoprogressive. The latter is an instance where systemic therapy has turned metastatic disease into a local problem. We don’t know how long this trick will last… but it can last a long time in some. While I have certainly treated folks in this case who promptly met-ed out, I also have some folks with long term DFS or slow metachronous disease that can be managed. Metastatic NSCLC, thyroid, NEC, p16+ H&N… can name 20+ folks off the top of my head. What was the alternative to RT?… uncontrolled dz.
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Sometimes a growing mass is the first of many, other times it is the only show in town for a while (until it seeds it’s own mets). Until we can tell which is which, why not err on the side of treating the growing tumor (assuming it can be done with minimal tox)? Less cancer is better (or so I hear)
I agree with you. Though I disagree that tox is nonexistent. It’s low but probably under-recognized.
The main problem arises when equipoise is lost.
Imagine if we never ran trials for BMT for breast cancer because people believed in it so much. Granted much more toxic than sbrt
Would you be willing to enroll oligometastatic or oligoprogressive patients on a randomized phase 3 trial comparing SBRT vs SOC? All I’m saying is that I am worried many are not willing, as this is problematic
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imagine if med oncs could get by on anecdotes!
I don’t think tox is always minimal (didn’t mean to imply as much)… I was saying IF the tox would be minimal (my constraints for oligoprogressive are a fair amount more strict
What is “SOC” with oligoprogressive dz? If it is just “observing” the growing mass, then you are correct about my lack of equipoise. I don’t think doing nothing is humane, unless treating would be morbid or the prognosis is otherwise poor.
dude - are you really arguing about this? we don't need trials? you don't think trials are even needed? what? and you're in academics?
no one is arguing that we can. we know we can.
the question we NEED to prove is if we should.
in the mean time - sure we all do treat, and we hope we are making a diff. but it may end up being in some or many clinical settings that we should not. Like breast oligomets and likely breast oligoprogression
and btw there are multiple randomized trials supporting single agent gem in metastatic NSCLC. it is a regimen that has proven itself to be something, even though we expect little of it.
no one is arguing that we can. we know we can.
the question we NEED to prove is if we should.
in the mean time - sure we all do treat, and we hope we are making a diff. but it may end up being in some or many clinical settings that we should not. Like breast oligomets and likely breast oligoprogression
and btw there are multiple randomized trials supporting single agent gem in metastatic NSCLC. it is a regimen that has proven itself to be something, even though we expect little of it.
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Humor me and answer my question
You have a patient with metastatic cancer who is progressing with ONE engaging mass and has no better systemic options, SBRT would be well tolerated… would you be comfortable doing nothing? Yes or no.
It’s a simple case we all see every day. Are you all withholding tx to wait for (another) RCT?
I also sbrt oligoprogressive disease, but someone could argue that 300x 10, 8 gy x1 etc is appropriate.
multiple of us have said we treat these patients. you keep asking a question that has already been answered and is totally irrelevant to the point.
literally 50% of the reported data (Breast from CURB) saying this is useless. and you don't even have a sense this may not help.
I definitely do NOT treat breast oligomets or breast oligoprogression with sbrt now.
I get that… my colleagues do this. I respect their skepticism, and they respect my idealism. I am upfront with my patients about the likelihood of distant failure.
I am a fan of EBM… but I am not an EBM purist. I am OK with the fact that some changes in practice won’t have an RCT to back them up.
I personally do not treat ANY breast patients because of the division of specialties where I work… but I admit that BR001 has made me more skeptical about the utility of RT in stage IV breast
what about when the EBM shows that the changes in practice dont help?
youll keep doing it for the lulz anyways?
thats big Nancy Lee energy
I will bet you a glass of bourbon that 5 years from now, observation will be SOC over PCI for LS-SCLC, without any RCT having completed accrual.
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Completely agree. And I would also add, that we may be paying "what a mole" because of diagnostics. When I started working, more than 15 years ago, diagnostic scans were not done so often as they are done today. Nowadays, med oncs send patients to CT/PET-CT every 2-3 months and the quality of these scans has also increased. We may be treating more, simply because we are able to see more small differences at shorter intervals than before.
What we should be doing is treating to improve outcomes for patients that matter to them.
Observing a nodule in the lung growing may be fine, if:
a) that growing nodule won't cause any symptoms
b) that growing nodule won't be the source of further disease progression/dissimination, which will in turn influence a patient-related outcome
There is a paradigm in the world of medical oncology, that once the next scheduled scan shows any progression, something must be done about it. We don't really know if local ablative treatment for oligoprogression should be the answer. After all, the definition of oligoprogression is tricky itself. What one defines as oligoprogression today, may be polyprogression tomorrow.
I will still give PCI, until I am proven wrong. PCI saves lives. 😎
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deleted1111261
If it’s saving lives, it’s because it isn’t PCI any more - it’s just treating brain Mets that slotman and others refused to image at work up! When the Asians staged with MRI, “PCI” didn’t work!
Man, palex why you gotta go there!
Im 2006, when we were zapping these, people said we were nuts. Now, nothing has changed - hardly any strong data - and saying if you don’t treat, that’s inhumane? Idk.. I get not being dogmatic, but challenging oncolore should require a study (“Metastatic disease is incurable”)
Man, palex why you gotta go there!
Im 2006, when we were zapping these, people said we were nuts. Now, nothing has changed - hardly any strong data - and saying if you don’t treat, that’s inhumane? Idk.. I get not being dogmatic, but challenging oncolore should require a study (“Metastatic disease is incurable”)
This is not correct.
PCI for LD-SCLC provides a survival benefit with a visible tail in long term follow up.
From the PCI metaanalysis, which is over 20 years old by now, PMID 10441603:
Even if there were macroscopic mets that were never seen, because noone scanned these patients, would PCI with 25/2.5 have controlled those macroscopic mets?
Nope. It would perhaps shrink them, but these patients would reccur down the road. 25 Gy giving over 2 weeks does not durably control macroscopic brain mets. PCI would have provided (perhaps!) a temporary OS benefit, but no long-term "cure" seen 5 years down the road.
It's the microscopic mets that PCI is meant to treat and eliminate. And it works as you can see in those curves!
Look at PCI as we view adjuvant chemotherapy for breast cancer. Treating sublinical disease.
And BTW: Slotman was ES-SCLC, not LD-SCLC.
Eliminating PCI for LD-SCLC is low hanging fruit. Noone likes it (apart from me and a few others, apparently!). Patients hate it, med oncs don't like it (I have heard some arguing against it based on data on WBRT for CNS-lymphoma, where they also hate it!) and most radiation oncologists don't like it. When the Japanese study came back showing that PCI for ES-SCLC did not help, there was a surge against PCI for LD-SCLC. There are however fundamental differences between PCI for ES-SCLC and LD-SCLC.
You want another example of low-hanging-fruit in radiation oncology? Total Body Irradiation for kids. NOONE likes that. The Europeans tried hard to abolist it and ran a huge, non-inferiority trial meant to prove that kids with ALL do not need TBI.
Total Body Irradiation or Chemotherapy Conditioning in Childhood ALL: A Multinational, Randomized, Noninferiority Phase III Study - PubMed
Improved OS and lower relapse risk were observed following TBI plus etoposide compared with chemoconditioning. We therefore recommend TBI plus etoposide for patients > 4 years old with high-risk ALL undergoing allogeneic HSCT.
pubmed.ncbi.nlm.nih.gov
The MAVERICK trial has a terrible primary endpoint and will likely come back positive because of that.
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deleted1111261
NO MRI STAGING for LS-SCLC
Not PCI. It’s just treating brain Mets. And it works!
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deleted1111261
Also, best way to have positive results on a study - have Slotman or Jeremic run the trial!
So you give 25/10 to your wbrt patients?
Giving WBRT with 25/2.5 to macroscopic mets is not curative treatment.
And sorry, I was editting my post, while u were replying. Perhaps you want to review it again.
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deleted1111261
It is an informative post. I’ve written about this on MedNet. There is no way I would choose that for myself. I would always give serial MRI and SRS salvage.
25/10 is low.
Look, have Jeremic and Slotman do a modern trial, modern systemic therapy, BID RT or >60 Gy if QD and PCI. If they are writing it, will be positive, and Bob’s your uncle, PCI will be proven in setting of modern oncology.
25/10 is low.
Look, have Jeremic and Slotman do a modern trial, modern systemic therapy, BID RT or >60 Gy if QD and PCI. If they are writing it, will be positive, and Bob’s your uncle, PCI will be proven in setting of modern oncology.
I am sorry, Simul, but you are not answering to the point that was made. I think highly of you, but:
a) telling me that you have "written about this on MedNet" as an argument
b) saying that "best way to have positive results on a study - have Slotman or Jeremic run the trial!"
are not what I had expected from you as a reply. Especially the second comment is not ok. I do not know if you have met these two colleagues or how you have formulated this opinion about them, but please do share your thoughts.
The argument is really simple.
If indeed the survival benefit shown in earlier trials on LD-SCLC with PCI was only because patients had macroscopic metastases, which were not picked up on baseline imaging - because no baseline imaging was performed - why did that survival benefit persist 5 years after treatment? Why is a clear difference in favor of PCI still visible there?
Is 25/2.5 enough to control macroscopic metastases and provide a survival benefit? I think not.
Thus, the argument is that the survival benefit is derived from controlling microscopic disease with PCI in the brain. Just like adjuvant chemotherapy controls microscopic disease in the liver in stage III colorectal cancer patients or in stage I-III breast cancer patients eligible for adjuvant treatment.
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deleted1111261
Meant to be a lot more light hearted than I sound.
Writing on MedNet about it is a joke. It’s just a question answer site. I’m no expert.
Slotman and Jeremic CRUSH it. I love their work. Just saying, they always have positive trials. Two people who I hope to meet one day.
PCI is standard of care. But, I caution using meta-analyses that don’t take into account modern treatment. Lots of butterfly effects.
But, yah- was lighter tone than came off! Sorry!
Agree with all of this… aside from some mixed feelings with PCI
One additional consideration is… the psychological element. Having untreated oligoprogressive disease makes many patients miserable.
When cancer is hopelessly metastatic and progressing, many patients can accept their imminent mortality because they can see the train coming down the tracks. Alternatively, when they have NED on imaging following definitive tx, they can occasionally treat themselves to the luxury of forgetting about their cancer. But one or two slowly enlarging masses… many really struggle with this -death isn’t imminent so no acceptance, but there is no forgetting about it either.
In my view, an added benefit of treating oligoprogressive disease definitively is that it can let some who feel this way have more time where they can just be themselves, even if they do end up becoming hopelessly metastatic -they can be NED just a little longer
Perhaps I overvalue this based on my own anecdotes… but I am sure we all do this in one way or another
By the way, @Palex80 @RealSimulD @jondunn @RickyScott @medgator, I enjoyed the debate.
These sorts of convos are impossible on Twitter these days… it’s refreshing to be able to argue a point here without worrying about career implications
These sorts of convos are impossible on Twitter these days… it’s refreshing to be able to argue a point here without worrying about career implications
No many radonc wouldn’t treat oligoprogressive disease (basically very little toxicity). I just “know” that the ones who don’t, and are most pro-ommission, also are the ones in favor of residency expansion etc.
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Need more docs to give less radiation
