CNS E14: Brain Metastases: Case-Based Review and Management Strategies

This episode is a mock oral boards session. I will present three distinct, challenging clinical scenarios. For each case, we will walk through the entire management process, from initial presentation all the way through treatment and follow-up, to sharpen your clinical decision-making.

Episode Transcript

(00:00):
Welcome to the Radon Smart Review CNS Cancer series.
Great to be here. Today we're sharpening our focus
on, well, a really critical and complex area in oncology, how we
manage brain metastasis. Yeah, absolutely.
It's a big one. We're.
Going to work through some challenging clinical scenarios.
The idea is to really strengthenyour decision making skills, get

(00:20):
you ready for comprehensive patient care, sort of like you'd
face in an oral board exam. Exactly.
And our mission today really is to take all this, you know,
sometimes complex information and distill it down, make it
memorable, actionable. We'll use real world cases,
throw in some practical tips. Just make sure you get a really
solid grasp on approaching diagnosis, planning, treatment

(00:42):
and the long term follow up for these patients.
OK, so let's start with the basics, the essentials,
understanding brain Mets from the ground up.
Now, we won't get totally lost in like super intricate
neuroanatomy, but it's vital to get where these lesions often
show up and why that location matters so much.
That's key. For instance, we'll talk about
cases in the left cerebellar hemisphere, even if you know

(01:05):
relatively small lesion there can cause major symptoms.
Yeah, because of Mass Effect, right?
Pushing on things like the 4th ventricle, messing with CSF
flow. That's a crucial foundation.
And then building on that, if you look at the bigger picture,
like epidemiology, brain Mets are a huge challenge, growing
challenge really. They come up so often.

(01:26):
So often and usually from commonprimary cancers, you know, in
the cases we'll discuss, you'll see how frequently primaries
like breast cancer, metastatic Melanoma and that specific lung
cancer type EGFR mutant non small cell, right?
NSCLC. Yeah, how often they lead to
disease in the brain. They make up a really
significant chunk of the patients we see.

(01:47):
So when a patient comes in maybewith new neurological symptoms
or sometimes even asymptomatic lesions just found on the scan,
which happens right, a thorough quick work up is just paramount.
So what's the absolute first step?
And are there any common like pitfalls to avoid?
Good question. With such a complex
presentation, the number one priority is always clinical

(02:09):
stabilization. OK, take our first case.
We'll discuss a 65 year old woman, progressive ataxia, so
trouble coordinating movements, plus nausea, Vertigo.
Classic symptoms. Classic cerebellar signs for her
job. One is high dose dexamethasone.
You've got to manage that cerebral edema, the swelling
around the tumor that causes so many of those acute symptoms.

(02:32):
So steroids first. Steroids first.
It can be a game changer. Really improve things quickly
neurologically. OK, stabilized.
Then what about imaging? What do we order right away?
You need that brain MRI with andwithout contrast immediately.
That's essential to really see the intracranial mass define it.
Got it. MRI.
And at the same time you need ACT of the chest, abdomen and

(02:54):
pelvis. The staging scans or.
The CTCK. P Exactly.
You have to restage, see if there's systemic disease.
The brain lesion might just be, you know, the tip of the
iceberg. Makes sense.
And performance status, that comes into play too, right?
Hugely her overall function. So in her case, she started with
a Karnovsky performance status KPS of 70.
OK, so needing some assistance. Right, but then it improved to

(03:16):
90 after steroids and maybe surgery.
That KPS score is a key prognostic factor.
It really influences what treatment options are even on
the table. And pathology if they do.
Surgery. Oh, absolutely.
Vital tissue is the issue, right?
So in our first case after resection pathology confirmed
metastatic adenocarcinoma and itwas consistent with her known

(03:38):
breast cancer primary that direct confirmation is goal.
The confirmation is fundamental,tells you the origin helps guide
systemic therapy. Precisely.
And we'll see later in another case with that EGFR mutant lung
cancer, how critical those molecular markers.
Oh yeah, for tailoring everything.
Systemic therapy, Radiation decisions, it all hinges on

(03:59):
those markers sometimes. OK, let's dive into this first
case, then really unpack it. So 65 year old woman solitary
enhancing 3.5 centimeter mass, left cerebellar hemisphere, big
lesion, big lesion, significant edema around it, Mass Effect
pushing on the 4th ventricle causing early obstructive
hydrocephalus. That's serious.
Yeah. And her staging C TS the CCTCIP

(04:22):
negative elsewhere. So just this one spot in the
brain, what's the initial management call here?
Given the size, the critical location causing symptoms that
hydrocephalus, my immediate recommendation is an urgent
neurosurgery consult right away,right away for maximal safe
resection. The powerful thing about surgery
here is it gives you the fastest, most effective
decompression. Relieves that pressure.

(04:43):
Exactly. It can reverse that neurological
decline quickly and like we said, you get that crucial
tissue for pathology. OK.
So she has successful surgery, gross total resection now as a
clean surgical cavity measures about 4 centimeters across.
Pathology confirms metastatic adenocarcinoma from her breast
cancer. Now what?
What's the adjuvant plan? OK, so post op my recommendation

(05:05):
is adjuvant stereotactic radiosurgery SRS to the
resection cavity. SRS To the bed, yeah.
SRS to the bed. It's that highly focused,
precise radiation. I would strongly argue against
just watching observation. Why?
Because the risk of it coming back right there local
recurrence is really high, like 50 to 65% at one year too high.

(05:27):
Wow. And critically, I would not
recommend whole brain radiation therapy WBRT.
OK, no WBRT. And this is where things have
really changed, isn't it? Massively this next point, it
really reshaped the field. There was the NCCTG NN70C trial.
In the 1070C right? That trial showed post op SRS
gives you equivalent overall survival compared to WBRT, but

(05:50):
with significantly less cognitive decline.
That's the key, the cognitive. That's the game changer.
You get the same Disease Controlwithout damaging the patient's
cognitive function nearly as much.
It's a fundamental shift to survival and quality of life.
So how do we actually plan that?SRS?
What's the setup? OK, for the planning, we'd
simulate her lying supine immobilized really well in a
custom thermoplastic mask. Got to be precise.

(06:12):
Extremely precise. Then we get a high resolution CT
scan with contrast and we fuse that with her post op MRI.
That fusion lets us see the target cavity perfectly OK.
But it's a big cavity. 4 centimeters isn't single shot
SRS risky there? Excellent point.
Yes, for a large cavity like that, giving the whole dose in

(06:32):
one single SRS fraction carries a pretty high risk of radiation
necrosis, you know, damage to the surrounding healthy brain.
So the key insight here is to use hypofractionated SRS.
Meaning multiple smaller doses. Exactly.
Deliver the radiation in smallerdoses over a few sessions, like
30 Gray in five fractions, or maybe 27 Gray in three

(06:53):
fractions. That approach significantly cuts
down the risk of necrosis, but it's still very effective.
Got it. Fraction for large cavities.
What's the actual target volume?The gross tumor volume.
The GTV is simply the surgical resection cavity itself on the
MRI. Then we add a small margin,
usually a 2mm isotropic margin, all around it that creates the
planning target volume or PTV. And why the margin that?

(07:15):
Margin's crucial It accounts fora microscopic uncertainty and
set up variations, and it's beenshown to improve local control.
The Stanford group showed that. OK.
And risks? What do we tell the patient?
Need to. Counsel them definitely acutely,
short term, maybe a fatigue headache, pretty common.
Long term, there's still that risk of radiation necrosis even

(07:37):
with fractionation for a large cavity, maybe around 10 to 15%
lower than single fraction, but not 0.
Still a risk. Still a risk.
And also maybe a slightly higherrisk of something called nodular
leptomeningeal disease, especially for resections in the
posterior fossa like the cerebellum, and particularly in
breast cancer patients. Something to watch for.

(07:58):
OK. And follow up after this SRS.
We'd get a baseline brain MRI maybe two to three months after
the SRS is done. Establish the new normal.
Exactly. Then keep doing MRI's every, say
three to four months for the first couple of years.
Just keep a close eye out for any recurrence or new spots.
All right, that covers the resecta lesion scenario really
well. Now let's pivot.
Yeah, different situation, multiple intact metastasis.

(08:21):
What do we do then? Good transition.
So consider this yeah, 45 year old man, metastatic Melanoma,
he's actually stable on combination immunotherapy, doing
well systemically OK, but his surveillance brain MRI pops up 3
new asymptomatic mats, small ones, 1.2 centimeters, 9
millimeters, 7mm. The KPS is good 90.

(08:42):
What's the recommendation for these intact lesions?
OK, multiple small asymptomatic mats in a patient doing well
Otherwise, my recommendation here is SRS alone to all three
lesions. Just SRS.
Just SRS, I would strongly advise against adding whole
brain radiation therapy. No WBRT.
And the justification for that? It feels like WBRT used to be
the standard for multiple mats. It did, but the evidence changed

(09:05):
things dramatically. This is based on Level 1
evidence, the Alliance N 0574 trial.
N-0574. That trial looked specifically
at patients with one to three brain Mets, and it showed very
clearly that adding WBRT to SRS results in significantly worse
cognitive deterioration. Significantly worse, and
critically, with absolutely no overall survival benefit.

(09:27):
So you're hurting their cognition for no gain in
lifespan. So the standard of care shifted
based on that. Completely shifted.
Preserving brain function becameparamount when survival wasn't
improved. That really highlights that
modern idea, right? That more isn't always better in
oncology. Exactly.
Sometimes less is more. And you know, if you look
deeper, there's a meta analysis by Sagal.

(09:49):
It's suggested for younger patients under 50, adding WBRT
might even be bad for survival. Really detrimental.
Potentially, it really forces you to weigh things.
Sometimes that less aggressive approach SRS alone actually
gives better long term outcomes when you factor in quality of
life and cognition. It's a powerful reminder.
Let's try an analogy for this. How would you explain SRS versus

(10:11):
WBRT simply? OK, think of SRS like a sniper.
A precision sniper. Good.
It targets only the known lesions.
The specific tumors with extremeaccuracy leaves the surrounding
healthy brain pretty much untouched.
Got it focused. Very focused.
WBRT on the other hand, it's more like a shotgun.
OK, wider spread. Yeah, it hits a much broader

(10:32):
area, gets the whole brain, including lots of healthy
tissue. So more collateral damage,
higher chance of those cognitiveside effects.
That's a great analogy. Sniper versus shotgun.
So for this Melanoma patient, how do you pick the SRS dose for
those 3 lesions? The dose is tailored to the size
of each lesion. We usually follow established
guidelines like the RTOG 9005 schema.

(10:55):
RTOG 9000. 5, right? So for example, for his 1.2cm
lesion, I'd probably prescribe 22 Gray.
For the two smaller ones, the 9mm and 7mm, maybe 24 Gray.
Higher dose for smaller lesions.Generally, yes, within limits.
They can tolerate a slightly higher dose per fraction and
these would typically be single fraction SRS.

(11:15):
Single shot for these small onesand the target volumes.
The GTV, the gross tumor volume is just the enhancing tumor
itself that we see on the MRI. Simple.
No extra margin like the CTV. For intact metastasis, typically
no CTV margin is used. We just define the visible
tumor, the PTV. The planning target volume would
then be the GTV plus a very small margin.

(11:36):
Maybe just one millimeter just accounts for tiny setup
uncertainties. And you mentioned controlling
dose to normal brain. Yes, critically important.
We watch the total volume of normal brain getting a
significant dose like 12 Gray, the V12.
We aim to keep that total V12 below 10 CC, 10 cubic
centimeters helps minimize that necrosis risk.

(11:57):
OK. And what about his
immunotherapy? He's on epilima, mabus and
nevilleumab. Do we stop it for SRS?
Ah, good question. Systemic therapy integration.
Based on data, particularly fromplaces like Johns Hopkins, it
seems there might be a synergistic benefit between
immunotherapy and SRS. They might work Better Together.

(12:17):
Potentially, yeah. And importantly, without a clear
signal of increased toxicity, atleast for this combination.
So you. Continue it.
My recommendation would be to continue his ipenivo without
interruption. Just proceed with the SRS
concurrently. Let the systemic therapy keep
working body wide while SRS hitsthe brain spots.
Makes sense risks to mention forthis patient.
Similar risks, mainly paralesional edema that's

(12:38):
swelling right around the treated spots and again
radiation necrosis, though the risk is generally lower for
these smaller single fraction treatments compared to large
cavities. OK.
And follow up still frequent MRI's.
Absolutely. Serial brain MRI is every two to
three months because even thoughwe're treating these three
spots, the risk of him developing new distant brain

(12:59):
metastases after SRS alone is still pretty high, maybe 50% at
one year. So you ZAP the ones you see, but
new ones can still pop up. Exactly, got to keep looking
all. Right, let's tackle our final
case. This one sounds like a classic
board question, a sequencing dilemma.
OK, let's hear it. 58 year old woman newly diagnosed with EGFR
mutant non small cell lung cancer.

(13:21):
EGFR positive. Her initial staging brain MRI
shows 8 asymptomatic metastases,all small, less than a
centimeter. Her KPS is good 90. 8 meds,
asymptomatic, EGFR positive. OK, the challenge, yeah, defend
two different evidence based management strategies.
How do you tackle that? Yeah, this is a great scenario
because there truly are two valid evidence supported

(13:45):
strategies. They're quite different though.
OK. What's strategy #1?
Strategy one is to defer radiation initially and lead
with systemic therapy. Start with drugs first.
Yes, specifically my recommendation would be to start
treatment with awesomemertinib. That's a targeted therapy at TKI
that works really well for EGFR mutations.
Hold the radiation in reserve. That seems counterintuitive for

(14:07):
eight brain Mets, even small ones.
Why awesomemertinib? First, what's the thinking?
It comes down to how well awesomemertinib works in the
brain. It has an exceptionally high
intracranial response rate. We're talking 65 to 70%, yeah.
That high inside the brain. That high?
So by starting systemic therapy first, you're treating not only

(14:27):
those eight known spots, but also potentially any microscopic
disease elsewhere in the brain or body that we can't even see
yet on scans. Treating the known and the
unknown. Exactly.
Then you'd get a follow up MRI pretty quickly, maybe in two to
three months, to see how well it's working intracranially.
OK, so that's strategy one awesome routine and 1st watch
closely. What's the second valid

(14:48):
strategy? The second strategy is the
opposite approach. Upfront stereotactic
radiosurgery hit all 8 lesions right away.
SRS to all 8 spots from the get go.
Yeah. This is also a very reasonable
approach. The justification comes partly
from the Yamamoto trial. Yamoto Trial.
Yeah, it basically showed that using SRS for even up to 10

(15:08):
metastasis can be feasible and effective as long as the total
tumor volume isn't too large. So number isn't the only factor.
Total volume matters too. Right.
And with eight small Mets, the total volume is likely low.
So this approach gives you immediate definitive local
control to all the sites you know about, zapping them right
at the start. Is there any other evidence
supporting upfront SRS here? There is a retrospective study

(15:31):
from Yale by Magnuson and colleagues.
CBL study it. Specifically looked at EGFR
mutant patients like this one and it suggested that getting
upfront local control with SRS followed by starting the TKI
like Aussie Martinib might actually lead to better overall
survival compared to TKI alone first.
Oh interesting, so maybe hittingthe hard locally first helps the

(15:52):
systemic therapy work better long term?
That's the hypothesis. So you see, you have two strong
evidence based paths with different philosophies.
Ossie Martinez first for systemic control or SRS first
for definitive local control. That's a true dilemma, and if
you chose upfront SRS, the planning would be similar.
Pretty similar yeah. SRS to all 8 lesions.

(16:13):
Doses would follow RTOG 9005 based on each lesion size, and
you'd have to be really careful about that cumulative dose to
the normal brain. That V12 keep the total V12 from
all 8 spots below that 10CC limit.
Right gets more challenging withmore targets.
Definitely requires meticulous planning.
OK, fantastic discussion of the cases.

(16:34):
Let's shift now and crystallize some key takeaways.
Time for some clinical pearls. All right, let's do it Pearl #1
For resected brain metastases, remember post operative SRS?
SRS to the cavity. Right, it offers equivalent
overall survival but significantly less cognitive
decline compared to WBRT. That's the NCCTG and 1070 C
trial take away. Prioritize cognition when

(16:55):
survival is the same. Excellent Pearl #2.
Pearl #2 for patients with limited brain Mets, say 1:00 to
3:00. SRS alone is the gold standard,
just SRS. SRS Alliance N 0574 gave us that
level 1 evidence. Adding WBDRT hurts cognition
doesn't help survival. Less is more.
Here for preserving brain function.

(17:17):
Got it. And Pearl #3.
Pearl #3 relates to that last case when you're dealing with
EGFR mutant non small cell lung cancer.
Brain meds. Remember how well targeted
therapies like osmertinib work intracranially.
They're high response rate in the brain.
Exactly that high response rate makes deferring radiation and
starting systemic therapy first a totally valid strategy.

(17:39):
But upfront SRS for local control is also very valid,
possibly even with a survival advantage.
Based on retrospective data, it highlights that sequencing
dilemma. Perfect pearls.
Ready for a quick board blitz Test our recall.
Let's go. Hit me.
Question 165 year old woman gross total resection of a
solitary 4 centimeter left cerebellar met from breast
cancer. What edge vent radiation

(18:01):
strategy is preferred to preserve cognition while
maintaining local control? And what's the key trial?
OK. Preferred strategy is adjuvant
hypofractionated SRS to the persection cavity.
Key trial supporting that is NCTG N170C.
Nailed it. Question 245 year old patient
metastatic Melanoma 3 asymptomatic brain Mets found on

(18:23):
surveillance. What's the evidence based
recommendation for initial management?
That would be SRS alone to all three lesions.
Evidence based on Alliance N 0574 showing no survival benefit
and worse cognition with added WBRT.
Excellent. Question 3, For that 4
centimeter surgical cavity, we talked about what type of SRS
regimen is appropriate to reduceradiation necrosis risk compared

(18:45):
to single fraction. Give me an example dose.
OK, for a large cavity you need hypofractionated SRS, not single
fraction. Example regimens would be like
30 Gray in five fractions or 27 Gray in.
Perfect, last one, question fourthat EGFR mutant lung cancer
patient with eight asymptomatic brain Mets all under a
centimeter. Name 2 valid evidence based
management strategies you could defend.

(19:05):
Two valid strategies are one defer radiation, initiate
awesome retina first banking on its high intracranial response,
two upfront SRS to all 8 lesions, aiming for immediate
local control supported by Yamamoto and potentially
magnusonial data. Fantastic.
You passed the Blitz. So that last question, it really
brings us right back to a major discussion point, maybe even a

(19:27):
controversy right now in the field.
How do we best sequence SRS and these amazing modern systemic
therapies, especially for these molecularly driven cancers like
EGFR mutant lung? It's such a fascinating and
evolving area. Like we discussed, starting with
a highly effective drug like ostomertine at first is
compelling. I know because it works so well

(19:48):
in the brain. Exactly.
Excellent CNS penetration, high response rates.
It could potentially delay or even avoid the need for
radiation for some patients. Plus it treats that micro
metastatic disease systemically.Makes a strong case.
But what's the argument for SRS first again?
Well, the flip side is that upfront SRS gives you immediate,
definitive local control of every spot you can see.

(20:09):
You know those are treated. Peace of Mind locally.
Right. And then there's that Yale data
from Magnuson suggesting maybe asurvival benefit if you do SRS
first, then the TKI. It's still debated retrospective
data, but it's out there. So the optimal sequence isn't
totally settled. Not completely settled and it's
a moving target as even newer drugs and combinations emerge.

(20:30):
It really requires individualized decision making.
OK, let's try to summarize what we covered today.
It was a lot, but really practical.
Yeah. I think we really solidified the
clinical reasoning for brain Mets management by working
through those 3 pretty challenging oral board style
cases. We definitely detailed the whole
process for a large symptomatic cerebellar MET surgery.

(20:51):
The importance of fractionated post op SRS Yeah.
And we strongly justified using SRS alone for that younger
patient with just a few intact Mets hitting hard on those key
trials about preserving cognition alliance.
And there are 574. Crucial trial and finally we
really debated the nuances of sequencing SRS and targeted
therapy specifically for that EGFR mutant lung cancer case

(21:14):
with many small Mets showed there are two good options.
Exactly. And the common thread through
all of this, I think is clear. Optimal management needs a deep
grasp of the evidence. You've got to tailor the right
treatment to the right patients.Always balancing that Disease
Control with preserving quality of life, especially cognitive
function. Couldn't agree more that balance
is key. Well, this has been incredibly

(21:35):
insightful for every listening. You can complete practice oral
boards and find more resources at Raton Smart learn.com.
That's RADONCSMARTL earn.com. Great resource.
And be sure to subscribe to RAD on Smart Review for our next
session. Thanks for tuning in everyone,
hope this was helpful.