Not radiating asymptomatic, limited brain mets

[seper]

For which scenarios leaving newly diagnosed mets untreated is a SOC?

a) melanoma starting immunotherapy combo
b) Her2+ breast cancer starting chemo+Herceptin
c) NSCLC starting chemo+Keytruda?

any other considerations?
thank you

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[Palex80]

Any patient with PS >2 ? Or let's just say "any patient who will most likely not benefit from RT due to his prognosis being quite limited".


You can add to the list:
a) treatment naive NSCLC with driver-mutation (although some data point out that oligo-brain-mets in this population may actually benefit from first line SRS)
b) treatment naive extensive disease SCLC

 

[BobbyHeenan]

I watch small cell brain mets if found at initial diagnosis (pre chemo).
Typically they improve with chemo. If anything there after chemo I SRS (assuming limited mets). Used to do whole brain after chemo but newer data/NCCN guidelines has shifted me to avoiding whole brain if possible in the above scenario.

*shoot, I missed Palex (b) above. agree, obviously.

 

[TheWallnerus]

As recent as 10y ago every rad onc dept would have a few whole brains under treat any and every given day. Now they’re rare as hen’s teeth.

 

[elementaryschooleconomics]

As recent as 10y ago every rad onc dept would have a few whole brains under treat any and every given day. Now they’re rare as hen’s teeth.

I was just thinking about this the other day.

When I started residency, one of the first things I was taught to do was bang out a WBRT plan as fast as humanly possible because it was a common consult.

I think I've done...maybe 2 in the last 4-6 weeks, everyone else is SRS.

 

[TheWallnerus]

I was just thinking about this the other day.

When I started residency, one of the first things I was taught to do was bang out a WBRT plan as fast as humanly possible because it was a common consult.

I think I've done...maybe 2 in the last 4-6 weeks, everyone else is SRS.

It feels like I’m down to two per six months!

 

[FrostyHammer]

Any patient with PS >2 ? Or let's just say "any patient who will most likely not benefit from RT due to his prognosis being quite limited".


You can add to the list:
a) treatment naive NSCLC with driver-mutation (although some data point out that oligo-brain-mets in this population may actually benefit from first line SRS)
b) treatment naive extensive disease SCLC

100% agree with the top portion. JCO paper in 2017 is retrospective but convincing to give for driver mutations, although with Tagrisso who knows. ED-SCLC may have a response to chemo +/- io but nearly all will eventually recur in the brain from what I've seen.

 

[evilbooyaa]

For which scenarios leaving newly diagnosed mets untreated is a SOC?

a) melanoma starting immunotherapy combo
b) Her2+ breast cancer starting chemo+Herceptin
c) NSCLC starting chemo+Keytruda?

any other considerations?
thank you

a) Phase II trials show a ORR of max of 50% with combination ipi/nivo. I would not omit RT in a patient eligible for SRS to all sites of intracranial disease. If a patient had so many brain mets that WBRT was only RT option, I would consider. I would advocate that all of these patients still be followed by Rad Onc with q2-3 month MRI.
b) I would not consider omission of RT in this scenario, either SRS or WBRT, off-prospective trial. What data is there in this space?
c) Similar to b. Where is the data in this space?

Any patient with PS >2 ? Or let's just say "any patient who will most likely not benefit from RT due to his prognosis being quite limited".


You can add to the list:
a) treatment naive NSCLC with driver-mutation (although some data point out that oligo-brain-mets in this population may actually benefit from first line SRS)
b) treatment naive extensive disease SCLC

a) As per the Magnusson paper, I would favor SRS in a patient eligible for it. Despite the magnusson paper that did see benefit of WBRT as well (although smaller magnitude), I would consider omission of WBRT in a newly diagnosed patient that is receiving Tagrisso (versus Tarceva as studied in Magnusson paper)
b) I would not omit RT, either SRS or WBRT as appropriate, in this scenario. What data is there in this space that looks at ORR and durability of response?

In terms of PS 2, I would consider omission of WBRT in a patient on death's door with NSCLC as per QUARTZ trial.

 

[thecarbonionangle]

If patient does not or likely not benefit from WBRT per QUARTZ then avoid RT. For other reasons, treat. It ain’t that complicated. Lets not write off our modality further from brain. It works well and it is generally tolerated very well.

 

[Palex80]

Well, the OP asked "For which scenarios leaving newly diagnosed mets untreated is a SOC?" which I interpret as:
For which scenarios would you not recommend brain radiotherapy upon diagnosis of brain mets.

This does not necessarily mean that one would not recommend to give brain radiation therapy "down the road", but simply not upon diagnosis, as in the immediate future.

So, concerning extensive disease SCLC:
Let's assume a newly diagnosed ED-SCLC comes up at the tumor board. He has a big primary tumor, mediastinal nodes and a bunch of liver mets on the PET-CT plus two asymptomatic 6 & 9 mm lesions in the frontal lobe on the cMRI. The med-onc says he wants to treat him with carboplatin/etoposide followerd by IO and thinks the patient is fit for full systemic treatment.
Would you recommend SRSing those lesions within the next couple of weeks? I wouldn't. Would you recommend WBRT now? I woulnd't.
I would let the med onc give his systemic treatment and ask for a cMRI upon completion of chemotherapy (that's in 3-5 months from now), when the patient would switch to maintenance immunotherapy.


As a rule of thumb, one can delay or ommit radiation therapy to the brain for asymptomatic brain metastasis if one of the following criteria apply:

a) the patient's prognosis is miserable and treating the brain mets will not help alter that. --> ommit RT.

b) there is a high chance that the brain mets will respond well to systemic treatment, but the prognosis of the patient is still not good despite a good ORR because PFS is still not good, meaning that extracerebral tumor progression may kill the patient before the brain mets grow again and become relevant --> defer RT and re-evaluate according to pattern of progression.

c) the patient's prognosis is actually good (usually due to a targettable driver mutation or chance of long-lasting remission with IO) --> possible to delay RT at first and re-scan after a couple of months. Go "all-in" from the start is the other argument which is supported by some (but not all data, as Evilboyaa well pointed out).



Actually, the question of delivering WBRT for newly diagnosed stage IV NSCLC with brain mets immediately or after systemic treatment has been asked before in a trial.

Primary chemotherapy for newly diagnosed nonsmall cell lung cancer patients with synchronous brain metastases compared with whole-brain radiotherapy administered first : result of a randomized pilot study - PubMed

Primary chemotherapy is more feasible and can be an appropriate option for patients with synchronous brain metastasis when neurologic symptoms or signs are absent or controlled. The role and timing of WBRT should be defined in further studies in this clinical setting.

pubmed.ncbi.nlm.nih.gov

[I know it's all pre-IO/TKI era].

 

[seper]

that's right! I'm not asking about WBRT. Mets are limited, but would anyone say SOC is to omit SRS in any of above scenarios?

 

[Radonc90]

Just an aside, as a verb = "irradiating", as a noun = "radiation or irradiation".

"Radiating" means let's say kidney stone pain radiating down to the groin.

Interesting that I learned this many many years ago from a nephrologist (before I even knew what radonc was).
The nephrologist was an English major and correctly pointed out to us (M3s at the time, when my classmate presented a case of kidney stone) the difference between "irradiating" and "radiating"...

 

[medgator]

that's right! I'm not asking about WBRT. Mets are limited, but would anyone say SOC is to omit SRS in any of above scenarios?

None imo, despite what some med oncs will try to sell. Defer maybe, but not omit

 

[TheWallnerus]

Just an aside, as a verb = "irradiating", as a noun = "radiation or irradiation".

"Radiating" means let's say kidney stone pain radiating down to the groin.

Interesting that I learned this many many years ago from a nephrologist (before I even knew what radonc was).
The nephrologist was an English major and correctly pointed out to us (M3s at the time, when my classmate presented a case of kidney stone) the difference between "irradiating" and "radiating"...

Ed Halperin would be very proud of you.

 

[Palex80]

None imo, despite what some med oncs will try to sell. Defer maybe, but not omit

Only instance would be patients with poor PS and very limited prognosis. No reason to treat them.

 

[seper]

Only instance would be patients with poor PS and very limited prognosis. No reason to treat them.

So, back to top 3 case examples - everyone would advocate SRS --> systemic management?
I keep seeing data about omitting SRS until progression but have not seen a definitive statement.

 

[Palex80]

So, back to top 3 case examples - everyone would advocate SRS --> systemic management?
I keep seeing data about omitting SRS until progression but have not seen a definitive statement.

Deferring is not omitting. I think that one can defer SRS in some of these patients without compromising the oncologic outcome.

And deferring does not necessarily mean "wait until progression", it can also mean to wait until response to first line systemic treatment can be evaluated and then reevaluate. Patients with extensive extracerebral tumir burden may not respond to systemic therapy (for instance BRAF-non-mutated melanoma with extensive liver mets) and never benefit from upfront SRS of asymptomatic brain lesions, dying within a few months from liver failure.

 

[Mandelin Rain]

Small asymptomatic brain mets in the setting of systematically advanced SCLC is the most common, imo.

If you’re really clenching your butt about it, just get a short interval scan after 2 cycles (6-8 weeks).

 

[seper]

Do SCLC brain mets really respond objectively to carbo/VP16? Not in a few cases that I remember, nor I'm aware of good data.

 

[medgator]

Do SCLC brain mets really respond objectively to carbo/VP16? Not in a few cases that I remember, nor I'm aware of good data.

Etoposide crosses the BBB and I've definitely seen mets shrink after a cycle or two of chemo

 

[TheWallnerus]

Do SCLC brain mets really respond objectively to carbo/VP16? Not in a few cases that I remember, nor I'm aware of good data.

All the time. Ymmv obv

Chemotherapy for brain metastases in small-cell lung cancer - PubMed

Chemotherapy, including the regimen of irinotecan and carboplatin, is an effective treatment for SCLC brain metastases.

pubmed.ncbi.nlm.nih.gov

 

[seper]

All the time. Ymmv obv

Chemotherapy for brain metastases in small-cell lung cancer - PubMed

Chemotherapy, including the regimen of irinotecan and carboplatin, is an effective treatment for SCLC brain metastases.

pubmed.ncbi.nlm.nih.gov

N=15 and chemo is irinotecan. Gotta be better data out there to support "all the time".
Anecdotally, I've seen folks wind up in the hospital with brain progression after 1-2 chemo cycles

 

[medgator]

N=15 and chemo is irinotecan. Gotta be better data out there to support "all the time".
Anecdotally, I've seen folks wind up in the hospital with brain progression after 1-2 chemo cycles

Definitely a case by case thing to defer... NCCN talks about that

 

[Palex80]

Why do we irradiate brain mets?

a) to comfort symptoms
b) to avoid complications
c) to enhance survival

a) Seems not be an issue here, since we are talking about small, asymptomatic mets.

b) May become an issue, if the mets are big or lie in critical areas of the brain. The thread starter mentioned "limited" mets. I do not know if one of them lies in the brain stem and if that were the case, I would also treat upfront with RT. If we are only talking about a couple of 2mm mets in the frontal lobe, I would be comfortable to defer RT in the above mentioned scenarios.

c) Is an issue in wide spread metastatic disease of the brain, mets in critical areas and if brain mets are the prognosis-defining tumor burden. This varies from case to case. I would be comfortable defering SRS of a 4 mm metastasis in the parietal lobe in a patient just diagnosed with a ES-SCLC with 20 liver mets and malignant pleural effusion, he has other issues to worry about.

Another consideration is how well systemic treatment will influence the brain mets. With a decreasing response rate to systemic treatment in the brain, the necessity for RT to the brain may grow.

 

[Neuronix]

I only defer SRS in the case of small brain mets and patient starting targeted therapies with very high response rates like osimertinib.

Otherwise, sometimes I will keep them on a short leash with frequent MRIs (q1.5-2mo) if the mets are tiny and especially if we are delaying whole brain radiation for diffuse brain metastases.

We have published and presented on stuff like this at conferences, but there really is no consensus or "standard of care" in this scenario.

 

[Grubbe-a-dub-dub]

I have a 36 yo patient with NSCLC who presented with innumerous brain mets - minimally symptomatic. Most mets are small.

Is it wrong that I want to wait for the Foundation NGS for an actionable mutation before proceeding with whole brain?

Unfortunately, it takes a while to get the results back but the patient wants to go on a short vacation anyhow (which I didn't argue with considering she just got diagnosed with stage IV cancer)...

I'm ready with a whole brain plan the second those results come back without an actionable mutation. For those wondering - hippocampal avoidance is probably not a great idea in this case since she has mets < 5mm from the hippocampus.

 

[medgator]

I have a 36 yo patient with NSCLC who presented with innumerous brain mets - minimally symptomatic. Most mets are small.

Is it wrong that I want to wait for the Foundation NGS for an actionable mutation before proceeding with whole brain?

Unfortunately, it takes a while to get the results back but the patient wants to go on a short vacation anyhow (which I didn't argue with considering she just got diagnosed with stage IV cancer)...

I'm ready with a whole brain plan the second those results come back without an actionable mutation. For those wondering - hippocampal avoidance is probably not a great idea in this case since she has mets < 5mm from the hippocampus.

Not a bad thought.... Could start on egfr/braf therapy etc if there is some actionable there but eventually i think you will be treating but maybe could turn it into an srt/srs case down the road if the response is good

 

[Palex80]

I have a 36 yo patient with NSCLC who presented with innumerous brain mets - minimally symptomatic. Most mets are small.

Is it wrong that I want to wait for the Foundation NGS for an actionable mutation before proceeding with whole brain?

Unfortunately, it takes a while to get the results back but the patient wants to go on a short vacation anyhow (which I didn't argue with considering she just got diagnosed with stage IV cancer)...

I'm ready with a whole brain plan the second those results come back without an actionable mutation. For those wondering - hippocampal avoidance is probably not a great idea in this case since she has mets < 5mm from the hippocampus.

No, it's not wrong. There is a risk of neurologic deterioration during this waiting time, but it's a risk I would take.
I do not believe in hippocampal avoidance anymore, especially not in palliation with WBRT.

 

[BobbyHeenan]

I have a 36 yo patient with NSCLC who presented with innumerous brain mets - minimally symptomatic. Most mets are small.

Is it wrong that I want to wait for the Foundation NGS for an actionable mutation before proceeding with whole brain?

Unfortunately, it takes a while to get the results back but the patient wants to go on a short vacation anyhow (which I didn't argue with considering she just got diagnosed with stage IV cancer)...

I'm ready with a whole brain plan the second those results come back without an actionable mutation. For those wondering - hippocampal avoidance is probably not a great idea in this case since she has mets < 5mm from the hippocampus.

Not wrong at all.
Worth making sure med onc has their ducks in a row too to VERY quickly order/insurance auth targeted drugs...if they’re slow that could be even more delay.

 

[Grubbe-a-dub-dub]

Not wrong at all.
Worth making sure med onc has their ducks in a row too to VERY quickly order/insurance auth targeted drugs...if they’re slow that could be even more delay.

Good point - didn't think of this.

 

[TheWallnerus]

I have a 36 yo patient with NSCLC who presented with innumerous brain mets - minimally symptomatic. Most mets are small.

Is it wrong that I want to wait for the Foundation NGS for an actionable mutation before proceeding with whole brain?

Unfortunately, it takes a while to get the results back but the patient wants to go on a short vacation anyhow (which I didn't argue with considering she just got diagnosed with stage IV cancer)...

I'm ready with a whole brain plan the second those results come back without an actionable mutation. For those wondering - hippocampal avoidance is probably not a great idea in this case since she has mets < 5mm from

I have a 36 yo patient with NSCLC who presented with innumerous brain mets - minimally symptomatic. Most mets are small.

Is it wrong that I want to wait for the Foundation NGS for an actionable mutation before proceeding with whole brain?

Unfortunately, it takes a while to get the results back but the patient wants to go on a short vacation anyhow (which I didn't argue with considering she just got diagnosed with stage IV cancer)...

I'm ready with a whole brain plan the second those results come back without an actionable mutation. For those wondering - hippocampal avoidance is probably not a great idea in this case since she has mets < 5mm from the hippocampus.

“HA is probably not a great idea...”

HA WBRT: more expensive than great

 

[evilbooyaa]

that's right! I'm not asking about WBRT. Mets are limited, but would anyone say SOC is to omit SRS in any of above scenarios?

I do not think there are significant enough delays with implementation of SRS to delay chemotherapy (or even give between cycles of chemo/IO). I would not omit SRS in any of those scenarios. I agree that med oncs may push for it and you may have to be flexible on your timing (say between C1 and C2 of Cis/Etop/Atezo in a ES-SCLC patient), but the data for complete omission is not there yet.

I have a 36 yo patient with NSCLC who presented with innumerous brain mets - minimally symptomatic. Most mets are small.

Is it wrong that I want to wait for the Foundation NGS for an actionable mutation before proceeding with whole brain?

Unfortunately, it takes a while to get the results back but the patient wants to go on a short vacation anyhow (which I didn't argue with considering she just got diagnosed with stage IV cancer)...

I'm ready with a whole brain plan the second those results come back without an actionable mutation. For those wondering - hippocampal avoidance is probably not a great idea in this case since she has mets < 5mm from the hippocampus.

I mean in a non-smoker that is at high risk for having EGFR or ALK mutation, then I would have a discussion with the patient and med onc about considering this and proceeding if all parties are comfortable. Document that the 'standard' is to WBRT now, but lots of nuance in an individual clinical situation.