Does periolesional edema influence dose prescriptin/fractionation for SRS brain mets?

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Kroll2013

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Dear colleagues,

I have an 80 years old patients known to have a lung adenocarcinoma since 2017, treated with systemic treatments and one course of brain SRS in 2017 with complete remission of the lesions.
he presents with two solitary brain lesions
one right frontal of 4mm
another right post parietal of 26 mm with intralesional hemorrhage and important peri-lesional edema (no midline shift ), inoperable

do you take in consideration the perilesional edema to decide for one Shot SRS or SFRT (27/3 for example?

Ty

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Do you take in consideration the perilesional edema to decide for one Shot SRS or SFRT (27/3 for example?

I often do, but it's more of a "gut feeling" than anything else. No hard evidence telling us that 3 x 9 Gy FSRT are better than 1 x 20 Gy SRS if you have edema.

There is a bias here. Considerable edema mostly comes from a metastasis of a considerable size. A 4mm metastasis is unlikely to cause so much edema, that will make you think about fractionating. A 26mm large one may however. And in fact, with a 26mm metastasis you are probably going to have difficulties to achieve a good V10 & V12 of normal brain tissue, so I would fractionate anyway...

There are two scenarios where I always fractionate:
a) a brain stem metastasis (although I know that many may do 1x16 Gy or 1x18 Gy, but probably noone will like to "push" to/beyond 20 Gy SRS)
b) a metastasis in the posterior fossa likely to cause obstruction of CSF flow due to its position. The "urban myth" that high single doses may lead to that metastasis swelling and making things worse prevails here. I always fractionate those, usually using 6 x 6 Gy. For example this one:
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Multiple ways to skin this cat. Many moons ago when the world was sane I mentioned this approach, a kind of old-school hybrid (whose oncologic outcomes weren't too shabby) sprinkled with modernity ("focal brain (IM)RT" vs WBRT). To re-iterate here are some theoretical advantages:
1) Can get tx started "immediately"
2) Starting w/ "gentle" fractionation vs "aggressive" fractionation may hold more favorable risk/benefit ratios in neuro-sx (ie some patients w/ edema) pts (YMMV)?
3) Shrinkage of tumor = smaller tx volume = better SRS all around
Needless to say, and I think we can all agree... brain mets are a very common clinical presentation with wide practice pattern variations.
(Also may need to consider keytruda in select patients ... I certainly don't see a downside to RT followed by keytruda in other words)
 
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I am a bit extreme but almost always do 27/3 for multiple lesions with single iso and immuno in almost every scenario
 
Multiple ways to skin this cat. Many moons ago when the world was sane I mentioned this approach, a kind of old-school hybrid (whose oncologic outcomes weren't too shabby) sprinkled with modernity ("focal brain (IM)RT" vs WBRT). To re-iterate here are some theoretical advantages:
1) Can get tx started "immediately"
2) Starting w/ "gentle" fractionation vs "aggressive" fractionation may hold more favorable risk/benefit ratios in neuro-sx (ie some patients w/ edema) pts (YMMV)?
3) Shrinkage of tumor = smaller tx volume = better SRS all around
Needless to say, and I think we can all agree... brain mets are a very common clinical presentation with wide practice pattern variations.
(Also may need to consider keytruda in select patients ... I certainly don't see a downside to RT followed by keytruda in other words)
The downside to Keytruda - offlabel - is hundreds of thousands in unnecessary medical costs in an era where cancer therapy will approach $200 billion.
 
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I’m confused about the idea of immunotherapy being questionable in this setting. Am I missing something? The only thing to consider is her age but if she’s fit enough for IO, she should get it. In addition to cranial radiation.
 
what’s a good resource to read to catch up on brain SRS. Would like to shore up my knowledge and hone some treatment techniques starting w some basics. It’s been a while
 
I’m confused about the idea of immunotherapy being questionable in this setting. Am I missing something? The only thing to consider is her age but if she’s fit enough for IO, she should get it. In addition to cranial radiation.
Simple, there's no phase 3 data. I'm not referring to the lung setting (there is phase 3 data for that) but rather the brain lesion. A 30% control rate for brain mets from a single arm phase 2 trial is not adequate. SRS that sucker!
 
Simple, there's no phase 3 data. I'm not referring to the lung setting (there is phase 3 data for that) but rather the brain lesion. A 30% control rate for brain mets from a single arm phase 2 trial is not adequate. SRS that sucker!

This is metastatic lung, read the post. Of course you SRS the met, but the patient does need immunotherapy or chemo immunotherapy depending on PDL1 starus. This is standard of care.
 
This is metastatic lung, read the post. Of course you SRS the met, but the patient does need immunotherapy or chemo immunotherapy depending on PDL1 starus. This is standard of care.
That's what I'm saying in my post above. No one will argue with immunotherapy for the met lung part, but I will sure argue against it if the brain met is the primary indication for immunotherapy. The brain met should be treated completely independently of whether/when immunotherapy is given.
 
I’m confused. The Brain Met IS the ‘met lung part’.

The Brain met is the primary indication for immunotherapy.

1) This patient has metastatic disease and needs systemic therapy
2) because there is a metastasis in the Brain, then yes also warrants local therapy
 
I’m confused. The Brain Met IS the ‘met lung part’.

The Brain met is the primary indication for immunotherapy.

1) This patient has metastatic disease and needs systemic therapy
2) because there is a metastasis in the Brain, then yes also warrants local therapy
I think you're confusing the indication for immunotherapy. The indication is "metastatic lung cancer" and most certainly not "brain metastases". There is randomized data for the former and not the latter. Hence my post above that brain SRS should be delivered for the indication of "brain metastases" regardless of what type of systemic agent is given for the "metastatic lung cancer".
 
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Dude. The Brain met is metastatic lung cancer and is an indication for systemic therapy. I hope you send these patients to a med onc after you treat
Them. Not sure what you’re doing.
 
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Dude. The Brain met is metastatic lung cancer and is an indication for systemic therapy. I hope you send these patients to a med onc after you treat
Them. Not sure what you’re doing.
Immunotherapy crosses CNS bbb well?

I get the point that you're trying to make, but unless there is systemic extracranial disease, probably not a lot of bang for the buck and prior to pd1/pdl1 era, med oncs would typically not give chemo in the situation of stage IV related to brain mets
 
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Dude. The Brain met is metastatic lung cancer and is an indication for systemic therapy. I hope you send these patients to a med onc after you treat
Them. Not sure what you’re doing.
That's not what I'm saying at all. I agree that it's semantically called "met lung cancer" because of the brain met, but those are 2 different diagnoses and management approaches. You give SRS for the brain met. And you give immunotherapy for the existing lung disease, other met foci, and micromet disease - not brain metastases.
 
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Just to be clear - after you SRS a patient you’re not going to send the patient to med onc for Immunotherapy?

Okay
 
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the patient has microscopic disease that you are not treating with SRS. Of course you send for consideration of systemic therapy, and especially in lung cancer when the patient is immunotherapy-naive.
 
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Just to be clear - after you SRS a patient you’re not going to send the patient to med onc for Immunotherapy?

Okay
I indeed would. That's not what I was referring to in the above posts though. What I was saying is that immunotherapy cannot be expected to address the brain mets adequately. Thus the necessity for SRS. The specific indication for SRS is brain mets, and thus the indication for immunotherapy is everything else other than brain mets.
 
I have an 80 years old patients known to have a lung adenocarcinoma since 2017, treated with systemic treatments and one course of brain SRS in 2017 with complete remission of the lesions.
he presents with two solitary brain lesions
one right frontal of 4mm
another right post parietal of 26 mm with intralesional hemorrhage and important peri-lesional edema (no midline shift ), inoperable

do you take in consideration the perilesional edema to decide for one Shot SRS or SFRT (27/3 for example?

Ty

I'd probably treat both with single fraction SRS (enhancing parts only of course) and manage edema with steroids. fSRS vs. SRS is unclear in this setting, though fSRS would not be wrong, especially to the big one (27/3 or 30/5 are typical doses).

Why is the parietal one inoperable? The hemorrhage makes me think of surgery both due to future hemorrhage and that they tend to have a lot of hard to control associated edema no matter what you do non-operatively. Radiation doesn't control brain met hemorrhage as far as I can tell. Make sure your imaging is very fresh when you treat because hemorrhagic mets can evolve rapidly.

100% agree to review and consider systemic options here after SRS. I don't know EGFR/ALK/ROS1 status, PDL1 expression levels, etc...
 
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Completely agree with Neuronix
 
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the only reason I broached the immuno subject above was the recent Lancet Onc article I had come across; we know some brain met patients get a CNS response from immunotherapy and it would appear logical at this point to consider immuno not just for its extra-cranial effects but knowing that for the properly selected patient it might control CNS disease as well. It's not a home run but it is not 100% ignoreable either.
 
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the only reason I broached the immuno subject above was the recent Lancet Onc article I had come across; we know some brain met patients get a CNS response from immunotherapy and it would appear logical at this point to consider immuno not just for its extra-cranial effects but knowing that for the properly selected patient it might control CNS disease as well. It's not a home run but it is not 100% ignoreable either.
I get what you're saying but unfortunately a near 3cm lesion expectorating edema is not the best case to "try and see how immunotherapy works". No one knows which patients get the best response intracranially to immunotherapy, other than those with higher PDL1 and smaller lesions (from another Lancet Oncol paper some yrs ago). Too many med oncs who think they can throw immunotherapy and defer local therapy which is the wrong answer, especially without randomized data and not particularly impressive phase II data either.
 
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I get what you're saying but unfortunately a near 3cm lesion expectorating edema is not the best case to "try and see how immunotherapy works". No one knows which patients get the best response intracranially to immunotherapy, other than those with higher PDL1 and smaller lesions (from another Lancet Oncol paper some yrs ago). Too many med oncs who think they can throw immunotherapy and defer local therapy which is the wrong answer, especially without randomized data and not particularly impressive phase II data either.

To speak for Scarb - he did not advocate for omitting radiation and giving immunotherapy alone.


You seem weirdly anti systemic therapy. This patient needs systemic therapy.
 
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the patient has microscopic disease that you are not treating with SRS. Of course you send for consideration of systemic therapy, and especially in lung cancer when the patient is immunotherapy-naive.
Btw Immunotherapy does not need to cross blood brain because it is not acting on the tumor but tcells? Only immunotherapy that actually binds to/ interacts with Tumor cells are pdL1 blockers?
Indication for immuno in solitary brain Met is 90% chance they have disease elsewhere in both body or brain and hopefully immuno is most effective when disease burden lowest.
 
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the patient has microscopic disease that you are not treating with SRS. Of course you send for consideration of systemic therapy, and especially in lung cancer when the patient is immunotherapy-naive.
Provided the patient has macroscopic, untreated disease, in my opinion.
There is no data showing an OS benefit in treating only microscopic disease in stage IV NSCLC with immunotherapy.
Strictly speaking, that is.
 
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Provided the patient has macroscopic, untreated disease, in my opinion.
There is no data showing an OS benefit in treating only microscopic disease in stage IV NSCLC with immunotherapy.
Strictly speaking, that is.

In theory, we all have microscopic cancer cells. Maybe we should take immunotherapy prophylacticly.
 
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Provided the patient has macroscopic, untreated disease, in my opinion.
There is no data showing an OS benefit in treating only microscopic disease in stage IV NSCLC with immunotherapy.
Strictly speaking, that is.

I thought the studies required measurable lesions, and brain mets didn't count as measurable lesions.
Reasonable to give. But, I think is considered off-label use, right?
 
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I thought the studies required measurable lesions, and brain mets didn't count as measurable lesions.
Reasonable to give. But, I think is considered off-label use, right?

Yes reasonable and what probably what everyone does.
 
To speak for Scarb - he did not advocate for omitting radiation and giving immunotherapy alone.


You seem weirdly anti systemic therapy. This patient needs systemic therapy.

Good thing you spoke for Scarb. He's notorious for holding back.
 
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To speak for Scarb - he did not advocate for omitting radiation and giving immunotherapy alone.
You seem weirdly anti systemic therapy. This patient needs systemic therapy.
Good thing you spoke for Scarb. He's notorious for holding back.
ha! we are giving immuno because it seems to work ... giving it, and thinking about it, in disease sites we haven't in the past.
Allow me to make the highly reasonable and likely posit that PD-L1 expressing NSCLC patients with brain mets who get SRS and anti-PD-L1 therapy will have higher long term CNS control rates than those getting SRS alone.
 
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ha! we are giving immuno because it seems to work ... giving it, and thinking about it, in disease sites we haven't in the past.
Allow me to make the highly reasonable and likely posit that PD-L1 expressing NSCLC patients with brain mets who get SRS and anti-PD-L1 therapy will have higher long term CNS control rates than those getting SRS alone.

YES
 
Provided the patient has macroscopic, untreated disease, in my opinion.
There is no data showing an OS benefit in treating only microscopic disease in stage IV NSCLC with immunotherapy.
Strictly speaking, that is.

...but there is for stage III.
 
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To speak for Scarb - he did not advocate for omitting radiation and giving immunotherapy alone.


You seem weirdly anti systemic therapy. This patient needs systemic therapy.
Yes, I got that, no need to speak for another person. My post referred to the posit that it "could have a benefit" without really knowing which patients it'll benefit, and likely not a near 3 cm one.
 
ha! we are giving immuno because it seems to work ... giving it, and thinking about it, in disease sites we haven't in the past.
Allow me to make the highly reasonable and likely posit that PD-L1 expressing NSCLC patients with brain mets who get SRS and anti-PD-L1 therapy will have higher long term CNS control rates than those getting SRS alone.
Until there are randomized data supporting that notion, I have little high-quality evidence-based reasons to do SRS alone (which I assume would be the control arm in your proposed trial).
 
...but there is for stage III.
Most of these stage III patients had macroscopic disease when entering the PACIFIC trial. Or do all your stage III patients have CR 14 days after completing CRT? ;)
 
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Allow me to make the highly reasonable and likely posit that PD-L1 expressing NSCLC patients with brain mets who get SRS and anti-PD-L1 therapy will have higher long term CNS control rates than those getting SRS alone.
But is that a valid endpoint to justify immunotherapy? You would have to show OS or decreasing neurological function or something else, that is actually clinically relevant.
Know what else produces higher long term CNS control rates? WBRT! We don't want to do that though, do we?
 
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This is the dumbest argument I’ve ever seen on this website

This patient needs to see medical oncology after you’re done, full stop.
 
This is the dumbest argument I’ve ever seen on this website
No need to get personal.

This patient needs to see medical oncology after you’re done, full stop.
I agree with you. This patient is very likely to show recurrent disease inside/outside of the brain. However, the indication to deliver "adjuvant" (it's not really adjuvant, but whatever...) immunotherapy is not backed up by data. There are no measurable lesions remaining after SRS and these patients (only brain disease, not extracerebral locations) were not enrolled in the registration trials for immunotherapy. Thus any suggestion on potential benefit by delivering immunotherapy now or only upon progression is speculative. That's it. And I expect that treatment should be discussed with the patient on the basis of these facts.
 
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Prophylactic immunotherapy! Works better than chloroquine!
 
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It’s not prophylactic. The patient has recurrent disease.

Palex is correct that patients with cranial disease only that then got treated locally weren’t in inclusion criteria of trials, but many of the trials also excluded patients with ANY brain mets at all (because these patients are deemed to have a poor prognosis and Pharma companies don’t want them in their numbers!) and these patients all get systemic therapy! And they should!

My mind is blown by some of you. I hope you’re just being difficult on the internet for the lulz, or overly academic for arguments sake, and in real life would appropriately refer to medical oncology.
 
Did I say I wouldn’t refer them, I think Palex also said he would... we’re just asking for the data. Somebody woke up in a pissy mood today, smile it’s Good Friday! The coronavirus pandemic will be over soon! 2 days to be exact.
 
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Until there are randomized data supporting that notion, I have little high-quality evidence-based reasons to do SRS alone (which I assume would be the control arm in your proposed trial).
Know what else produces higher long term CNS control rates? WBRT! We don't want to do that though, do we?
There are no measurable lesions remaining after SRS
There are, depending on the moment in which you take the measurement, 100% measurable lesions after SRS. That is to say, get an MRI the day after SRS, 100% of those SRS'd lesions are still hangin' around. Now 90+% of them are "dead men walking lesions" and doomed to regress... but a fraction aren't. An unpredictable fraction. But send all your SRS patients over the med onc the day after SRS, and if he/she gets an MRI on the patient... "Sir you still have a brain met and I want to give you keytruda."

I'm being completely silly in my analogy but you get the point. There will be some SRS patients well after the SRS who have measurable brain mets and the med oncs will want to give them immuno specifically for the brain mets. We know keytruda works for some NSCLC brain met patients (and has a response rate of x%), and we know SRS works for some brain met patients (and has a response rate of y%). What I have yet to see happen in oncology (has it ever happened?) is when two separate, disparate treatments have been tried in a disease, given response rates "x" and "y" with y being greater, that x+y<y. At worst, x+y=y. But usually, almost always, x+y>y; it's been a rather predictable thing. (You can make this x+y>y argument about WBRT+SRS; but then we get into wholly valid toxicity concerns, risk/benefit ratios etc.)
 
There are, depending on the moment in which you take the measurement, 100% measurable lesions after SRS. That is to say, get an MRI the day after SRS, 100% of those SRS'd lesions are still hangin' around. Now 90+% of them are "dead men walking lesions" and doomed to regress... but a fraction aren't. An unpredictable fraction. But send all your SRS patients over the med onc the day after SRS, and if he/she gets an MRI on the patient... "Sir you still have a brain met and I want to give you keytruda."
Interesting interpretation. Let me twist it a bit further.

Mr. Miller has a brain met from NSCLC. Mr. Miller get's SRS.
Mr. Miller gets immunotherapy, since his brain met is still visible in the MRI 4 weeks post SRS.

Mr. Smith has a brain met from NSCLC. Mr. Smith gets surgery, followed by SRS to the cavity.
Mr. Smith does not get immunotherapy, since his brain met is not visible in the MRI 4 weeeks post surgery/SRS.

Does that make sense?

I'm being completely silly in my analogy but you get the point. There will be some SRS patients well after the SRS who have measurable brain mets and the med oncs will want to give them immuno specifically for the brain mets.
Brain mets on early MRI post SRS behave differently in a patient to patient basis without clear clinical implications. If you perform an MRI 4 weeks post SRS you may find the same brain met you treated before, you may find a bigger brain met, you may find a brain with less contrast enhancement, you may find no brain met. Yet, all these patients usually have the same prognosis, since MRI 4 weeks post SRS usually says little about the vitality of the brain met. In 99% of cases you will rescan in a patient without symptoms and not draw ANY therapeutic consequence irrelevant of the scan's result. The reason we do the stupid scan is to make sure another brain met has not popped up. But the scan itself is more or less useless at 4 weeks for the brain met that was treated.

We know keytruda works for some NSCLC brain met patients (and has a response rate of x%), and we know SRS works for some brain met patients (and has a response rate of y%). What I have yet to see happen in oncology (has it ever happened?) is when two separate, disparate treatments have been tried in a disease, given response rates "x" and "y" with y being greater, that x+y<y. At worst, x+y=y. But usually, almost always, x+y>y; it's been a rather predictable thing. (You can make this x+y>y argument about WBRT+SRS; but then we get into wholly valid toxicity concerns, risk/benefit ratios etc.)
I never said that Keytruda will not provide a higher response rate. It will likely do so. Yet, is radiologic response rate a valid endpoint? Is it a meaningful endpoint for the patient? Why haven't we been giving the patients chemo in the past for exact the same scenario? A cisplatinum-doublet will also provide a X response rate in the brain.
Unless you can PROVE that Keytruda will ENHANCE overall survival in patients with ONLY brain mets who are getting Keytruda post SRS of all brain mets, over giving Keytruda at progression, there is no clear indication for immunotherapy in this setting.
 
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