CNS E08: LGG Part 3: Treatment Planning & Case-Based Review

This is Episode 8: Low-Grade Glioma Part 3: Treatment Planning & Case-Based Review. Over the last two episodes, we've built the complete evidence-based framework for managing WHO Grade II gliomas. We've learned how to risk-stratify patients, when to treat, and what regimen to use. Today, we put that knowledge into practice. We'll start with a deep dive into the technical details of treatment planning and toxicity management. Then, we will consolidate our knowledge by working through a series of challenging, oral board-style case scenarios designed to test your clinical decision-making from start to finish.

Episode Transcript

(00:00):
Welcome to the rad on smart Review CNS cancer series.
Today we're tackling a really critical and often quite nuanced
topic in neuro oncology, the management of low grade gliomus.
And this isn't just about, you know, memorizing facts.
It's really about building a solid framework for making
precise clinical decisions for, well, a pretty unique patient

(00:21):
population. That's exactly right.
Over the next session or so, we're going to walk through
pretty much everything from the initial diagnosis and the latest
kind of molecular insights all the way to the really intricate
details of treatment planning. And you know, those real world
case scenarios you'll definitelyencounter.
And we'll try to solidify understanding with some maybe

(00:41):
challenging clinical decision making examples that should feel
pretty close to oral board. That's exactly our goal here is
to give you that comprehensive understanding, kind of putting
all that foundational knowledge into practice, exploring how to
precisely plan radiation and manage potential toxicities,
Really make sure you feel confident and prepared.
So let's maybe start by setting the stage for World Health

(01:03):
Organization or WHO grade 2 gliomas.
What immediately stands out about these tumors and, you
know, patients who typically present with them?
Well, what's immediately striking, I think, is the
patient population itself. We're often dealing with
relatively young individuals, sometimes, you know, in their
20s or 30s. They often have really long life
expectancies ahead of them. And this fact, it profoundly

(01:25):
shapes our approach. It means minimizing those leat
toxicities, things like neurocognitive decline, hormonal
issues, or even the small risk of secondary cancers.
It becomes just as crucial as achieving excellent tumor
control. It's a real balancing act.
It's a very delicate balance, yeah, where quality of life is
just paramount alongside the oncologic outcomes.

(01:46):
That distinction is so key because unlike say, higher grade
tumors that might demand immediate really aggressive
intervention, these low grade gliomas, just by their nature,
they often don't show rapid enhancement on scans.
They're often slow growing, which kind of means our
diagnostic workup has to be incredibly thorough, right, to

(02:07):
truly understand what we're dealing with.
It absolutely does when we suspect a low grade glioma, the
initial workup is just foundational.
It always starts with a really comprehensive history and
physical examination. We need to confirm the patient
has ideally no residual neurologic deficits and
maintains A carnosity performance status or KPS of
100. You know, patient with symptoms

(02:27):
or functional deficits, even mild ones, that might influence
our timeline for intervention. And imaging well as always in
neuro oncology, it's just non negotiable, isn't?
It indispensable, yeah. We need both preoperative and
postoperative magnetic resonanceimaging or MRI scans.
These are vital not just for diagnosis but also to confirm
the extent of surgical resection.

(02:49):
But the real game changer in recent years, I think the piece
that often holds the most weightis the final integrated
pathology report. We absolutely need to know The
Who grade, the isocitrate dehydrogenase or IDH mutation
status, and crucially the 1P and19 Q Co dilution status.
Those are key. And this isn't a decision made
in a vacuum, either. It's a team effort.

(03:11):
Not at all. It truly necessitates A robust
multidisciplinary discussion. You know, a referral to neuro
oncology is almost always a given.
It brings in the surgeons, medical oncologists and often
neuropathologists to weigh in. Every perspective really helps
refine the plan. OK.
So once we have all that rich information, the next critical
step is risk stratification for these low grade gliomas.

(03:32):
How do we use criteria like the The Pagliotti criteria to guide
our decision making thinking about factors like age,
resection extent, tumor size, midline crossing?
Well, that leads us right into the pathology, which has seen
some truly transformative updates recently.
What's really fascinating, I think, is how specific
pathological features and these molecular markers are now

(03:54):
fundamentally driving our understanding and treatment
decisions. It's far beyond just what we see
under the microscope now for WHOgrade 2 gliomas, the IDH
mutation status and that 119 Q code deletion status are, like
you mentioned, absolutely critical.
They're just central to the modern classification.
But there's that one molecular marker that if it's present, it

(04:15):
just completely rewrites the story of the tumor, doesn't
matter what else. You see, you've absolutely hit
on the most impactful change, the homozygous deletion of the
CDK and 2A and B gene. This isn't just, you know, a
slight adjustment in classification, It's a profound
molecular discovery. It tells us these tumors, even
if they initially look like a totally benign grade 2 under the
microscope, they harbor an aggressive, really high risk

(04:38):
biology. This finding automatically
upgrades a tumor to an astrocytoma IDH mutant WHO grade
4, regardless of any other clinical factors.
It just fundamentally alters ourtreatment strategy.
Maybe from watchful waiting straight to immediate aggressive
intervention. It's a stark reminder that what
we see on a scan isn't always the full story.
The genetics are kind of the real crystal ball these days.

(05:01):
So OK, with all that crucial diagnostic information in hand,
let's shift gears a bit to the meticulous process of modern
radiation planning for these lowgrade gliomas.
Given the patient profile we discussed.
Young, long life expectancy Precision here isn't just a
goal, it's paramount. Or it absolutely is.
Yeah, let's let's walk through the steps.
Maybe imagine you're sitting down to plan one of these cases.

(05:24):
It starts with the CT simulation.
We immobilize the patient supineposition, typically with a
custom thermoplastic mask that ensures reproducibility
day-to-day. We acquire a thin slice contrast
enhanced computed tomography or CT scan.
But here's where the art and science really merge the image
fusion. This is arguably the most

(05:45):
critical step. You must fuse the planning CT
with the patient's diagnostic MRI scans.
For a low grade glioma this requires at a bare minimum the
post operative T2 fell air sequence.
And really as best practice you should always try to fuse the
preoperative MRI as well. It helps you fully appreciate
the original tumor extent beforeany surgical changes, you know,

(06:08):
gives you that complete picture of the disease.
Got it. So when it comes to defining the
gross tumor volume, the GTV for low grade gliomas, it's a
different ball game compared to say a glioblastoma where you
might be looking for that brightcontrast enhancement.
That's a crucial distinction. Yeah.
The cardinal rule really of low grade glioma planning is that
for these typically non enhancing tumors, the entire T2

(06:30):
and flare hyperintense signal represents the gross tumor.
You can almost imagine like a specific type of MRI image where
the tumor, even if it's not obviously glowing with contrast,
it lights up subtly, almost likea faint Halo that shows us its
full extent, including any sort of hidden tendrils.
So your GTV should be a really careful contour of this
abnormality and importantly including the surgical cavity.

(06:52):
From there we create the clinical target good volume or
CTV landmark trials like RTOG 9802 and your RDC 23 three.
They used CTV margins of about 1to 2cm In modern Intensity
Modulated Radiation therapy, or IMRT, a 1.5cm isotropic
expansion from the GTV is prettymuch a widely accepted standard

(07:15):
now. And the CTV isn't just a simple
geometric expansion, is it? You have to be incredibly
thoughtful about the anatomy around.
It absolutely. The CTV is really an anachomical
concept, so it has to be edited or trimmed to respect the
natural barriers to tumor spreadin the brain.
A good mnemonic to remember is that gliomis generally respect
BDT. That's bone dura in the

(07:36):
tantorium BDT. Yeah.
So you should trim the CTV flushwith the inner table of the
skull, the Falk cerebri, that tough membrane dividing the
hemispheres and that tantorium cerebelli, that sort of tent
like structure over the cerebellum.
Think of them like natural fences in the brain.
Makes sense. But there's a vital exception to
that trimming rule, isn't there?One that can really trip you up
if you're not careful. Indeed there is, and it's

(07:57):
critical for board exams and more importantly, patients and
safety. You must not trim the CTV at the
corpus callosum if the tumor is nearby.
Why is that? Because this is a primary route
for contralateral spread, it's basically a super highway for
tumor cells between the hemispheres.
So we absolutely cannot assume it acts as a barrier.
You have to include it. Got it.

(08:17):
No trimming at the corpus callosum if the tumor is closed.
Exactly. Then after the CTV we define the
planning target volume or PTV. This is a geometric expansion,
usually about 3 to 5mm, just to account for set up uncertainty,
tiny day-to-day variations, and unlike the CTV, the PTV should
not be trimmed. OK, so to put it simply for for

(08:40):
our listeners, when we talk about the PTV, it's almost like
we're building a little safety net around the tumor, right?
Like imagine you're trying to hit a bull's eye, but you know
your hand might shake a tiny bitor maybe the target might wobble
slightly. The PTD is that extra bit of
space you aim for just to make sure you definitely cover the
entire bullseye, accounting for those slight movements or maybe

(09:01):
inaccuracies during treatment delivery, just ensuring the
whole target gets the intended. Dose that's a perfect analogy?
Yeah, exactly. And the standard prescription
for low grade gliomas is typically 50.4 Gray up to maybe
54 Gray delivered in 1.8 Gray fractions.
And this isn't just some arbitrary number, it's really
based on definitive negative dose escalation trials, things

(09:22):
like EOE CC-22844 and NCC TG867251.
Right, the dose escalation trials.
Yeah, they definitively showed that higher doses just increased
toxicity without any survival gain.
So in this case, more isn't better, it's just more toxic. 54
Gray Max Got it. So we're not just, you know,
blasting away. We're being very mindful of

(09:43):
protecting those surrounding structures that are critical for
patient function and especially quality of life long term.
What are some of those key organat risk or OAR constraints we
absolutely need to have memorized like the must nose?
For sure, you definitely need toknow these cold for exams and
practice. We aim to keep the brainstem D
Max the maximum point dose less than 54 Gray.

(10:05):
Same for the optic chiasm and optic nerves D Max less than 54
to 55 Gray. That's crucial for preserving
vision. Then hearing.
The mean dose to at least one cochlea should ideally be less
than 45 grey. But honestly, for these young
patients, we always strive for less than 35 greys if we can to
protect hearing as much as possible.

(10:27):
And vitally, the lens D vac should be kept below 10 grey.
That's to minimize the risk of cataracts developing later on.
Makes sense. So beyond just the technical
planning, counseling patients about potential toxicities is
obviously a huge part of the process, especially for a
condition like this that really effects long term quality of
life. What do we quickly discuss with
patients regarding, say, acute versus late effects?

(10:48):
Right, we cover both. The acute toxicities are
generally pretty mild and transient.
Things like fatigue, some temporary hair loss just in the
treatment field, maybe mild skinredness or erythema.
These usually resolve pretty quickly after treatment finishes
OK. The late toxicities though,
those are our primary long term concern.
Neurocognitive decline is often the most feared effect, and

(11:10):
honestly it's a main reason we might choose to defer radiation
therapy when observation is a safe initial option.
Radiation necrosis is another one.
It's rare thankfully, but can beserious.
The risk is catch very low by sticking to that 54 grey maximum
prescription. There's also a risk of
endocrinopathy, hormone problemsif the hypothalamus or pituitary

(11:32):
gland are within or near the radiation field.
And finally, there's a small butreal lifetime risk of a
radiation induced second malignancy.
So balancing those risks againsttumor control, that's an ongoing
conversation with the patient. Absolutely.
It's a continuous dialogue. All right.
Now that we've laid quite a bit of groundwork, let's move into
our clinical decision making segment.

(11:52):
This is where we really apply all this knowledge to some
challenging kind of oral board style case scenarios.
Think of these as your practice questions.
OK, let's dive into case one. Imagine you've got a 32 year old
architect, you know prime of hiscareer, who presents to the
emergency department after his first ever focal seizure.
An MRI reveals A3 centimeter nonenhancing mass with some subtle

(12:14):
calcifications up in the right frontal lobe.
He undergoes a gross total resection.
You are the first oncologist to see him post op.
What are the key components of your initial work up and
consultation for this patient? OK.
So first step is always a meticulous complete history and
physical exam. I need to confirm he has no
residual neurologic deficits andhopefully KPS of 100.

(12:36):
I'd absolutely ensure I have allthe necessary imaging,
specifically both the preoperative and the
postoperative MRI so I can confirm the extent of that
resection myself. But the absolute bedrock here,
the most crucial piece is that final integrated pathology
report. I need to know The Who grade,
the IDH mutation status and that119 QO code deletion status.

(12:57):
And of course this needs a multidisciplinary discussion.
Neuro oncology referral is nonnegotiable.
Excellent. OK, so the final pathology
report comes back oligoden druglioma IDH mutant 1P and 19 Q
code deleted. WHO grade two.
He has that KPS of 100, no neurologic deficits.
Given this information, what arehis management options and what

(13:19):
would you recommend? Right.
So this patient presents as a pretty clearly low risk grade 2
glioma. I'd use the Pagnotti criteria to
risk stratify him. He's under 40, he had a gross
total resection and he has the favorable oligo to drove glioma
Histology with the code lesion. Critically, he has 0 high risk
factors. Therefore, my primary
recommendation would be active surveillance with serial Mr. is

(13:41):
OK. And your justification?
I justify this based on the low risk observation arm of the RTG
98-O2 trial that showed A5 year progression free survival of
roughly 50% for similar patientsmanaged with observation low
initially. So I would counsel in this is a
safe initial approach, but it absolutely requires diligent
lifelong monitoring and importantly there is a

(14:01):
significant chance he will need active treatment down the road.
We need to be upfront about that.
Perfect rationale. OK, let's move to a more complex
scenario now. Case 2, Your next patient is a
50 year old man. He presents with several months
of worsening headaches and some subtle word finding difficulty.
An MRI reveals a large 7 centimeter non enhancing T2
flare, high hyperintense mass inhis left temporal lobe.

(14:23):
It's extending into the insula and O crossing the midline via
the corpus callosum. A subtotal receptionist
performed the diagnosis. Comes back astrocytoma IDH
mutant WHO grade two. He has ongoing mild dysphasia
post op. What is your initial treatment
recommendation here? OK.
This patient unequivocally has ahigh risk grade 2 astrocytoma.

(14:43):
He takes multiple Pignati risk factors, age over 40, tumor size
well over 6 centimeters and crucially it's crossing the
midline. So the standard of care for high
risk low grade glioma is combined modality therapy and
that's firmly rooted in the results of RTOG 98-O2.
I would recommend immediate adjuvant radiation followed by
chemotherapy. Given his ongoing symptoms in
the high risk features, deferring treatment just

(15:04):
wouldn't be appropriate here. That's a very clear rationale.
OK, The patient agrees to proceed with your
recommendation. Could you outline your radiation
treatment plan in detail for him?
Sure, my prescription would be 54 Gray delivered in 30
fractions. So 1.8 Gray per fraction.
I justified this dose based on those definitive negative dose
escalation trials. We talked about EOTC 22844 and

(15:27):
NCCTG 867251 which showed higherdoses just add toxicity.
No survival benefit for the GTV.It's the entire T2 and full
layer abnormality seen on the preoperative MRI.
Making sure to include the surgical cavity from the post op
scan. The CTV is then a 1.5cm
isotropic expansion on that GTV and a critical point for this

(15:50):
specific case given his tumor involves the corpus callism, I
would not turn the CTV at the midline.
We need to ensure that common pathway of spread is fully
treated. Very important.
Point exactly. The PTV would then be a standard
3mm expansion on the CTV to account for setup.
A very thorough plan. And what about your chemotherapy
recommendation for this particular patient?
So following the radiation, I would recommend adjuvant

(16:10):
temazolamide or TMZ. Now historically RTUG 98-O2 used
PCV chemotherapy. However, the more recent cannon
on trial which specifically looked at anaplastic
astrocytomas should a clear survival benefit with adjuvant
TMC, right? That was important data.
Yeah. And given the significantly
better toxicity profile of TNC compared to PCV, it's now

(16:34):
generally the preferred agent for IDH mutant astrocytomas like
this one. The standard regimen will be up
to 12 cycles, typically dosed at150 to 200 milligrams per meter
squared for five days every 28 days.
Excellent. OK, let's discuss our final
patient scenario. Case 3.
This is a 35 year old woman. She underwent a gross total

(16:54):
resection of a tumor that appeared on imaging and initial
Histology to be a pretty standard grade 2 astrocytoma.
However, the full molecular panel comes back shows an IDH
mutation, ATRX loss and critically A homozygous deletion
of the CDKN 2A and B gene. Clinically, she's doing great
asymptomatic with the KPS of 100.
How does this specific molecularfinding completely change her

(17:15):
diagnosis and her subsequent management?
Wow, OK, this is truly the type of case that just perfectly
highlights the revolution in neuro oncology diagnostics.
That homozygous deletion of CDK and 2A and B.
It's a major high risk molecularmarker per the 2021 WHO
classification. That finding automatically
upgrades her tumor diagnosis to an astrocytoma IDH mutant WHO

(17:38):
grade four, grade four, grade four.
Yeah, she doesn't have low gradeglioma anymore, despite what the
initial Histology might have suggested.
She has a molecularly defined grade 4 tumor, and that means
her prognosis is unfortunately far worse than what a typical
grade 2 or even grade 3 astrocytoma would suggest.
It basically tells us her tumor is biologically very aggressive.
That's precisely it. So given this profound

(18:00):
classification based on the moleculars, what is your
treatment recommendation for hernow?
Well, because she now officiallyhas AWHO grade 4 tumor
observation is absolutely inappropriate even despite her
favorable clinical factors like the gross total resection and
being asymptomatic. Now, while there isn't a
specific perspective trial for this exact molecular entity yet,

(18:22):
given its aggressive biology, which really closely mirrors
that of standard IDH mutant glioblastoma, the most
appropriate course is to extrapolate from the
glioblastoma treatment paradigm.So I would recommend the full
stop protocol that involves radiation, but 60 Grays and 30
fractions this time higher dose,higher dose, Yeah, with
concurrent daily TMZ key with therapy followed by 6 to 12

(18:42):
cycles of adjuvant TMZ. And her radiation planning
philosophy would also shift. We follow GBM principles where
the GTV is typically defined by the surgical cavity and any
residual T1 enhancement and a 1.5 centimeter CTV margin is
used. But that CTV generally excludes
the surrounding T2 fell air edema.
Unlike in low grade planning, it's a different approach.

(19:03):
Excellent reasoning. These cases truly under score
that journey from basic knowledge to really complex
clinical application, especiallywith the molecular data now.
So now let's maybe distill some clinical pearls, those concise
high yield takeaways that will hopefully stick with you for
your boards and more importantly, for your practice.
OK Pearl number one for low grade gliomas, always remember

(19:25):
the tumor volume for contouring the GTV is defined by the T2 and
L feller hyper intense signal, not T1 enhancement.
That's a fundamental distinctionfrom glioblastoma planting.
Don't mix them up. Pearl #2 While gliomas generally
do respect natural anatomical barriers, remember BDT bone dura
tantorum. The critical exception that
super highway of spread is the corpus callosum.

(19:48):
Always remember to include it inyour CTV if the tumor is nearby.
It's a very common pathway for contralateral spread.
Parole #3 based on those major dose escalation trials we
mentioned, 54 grade remains the standard maximum dose for low
grade gliomas. Higher doses were definitively
shown to increase toxicity without improving survival
outcomes. So again, more is not always
better here. And finally, Pearl #4 the 2021

(20:11):
WHO classification brings in these powerful molecular
markers, like the homozygous deletion of CDK and 2A and B.
That single finding can instantly upgrade a tumors
grade, completely changing the management plan even in patients
who look clinically favorable. Otherwise, it unmasks that
underlying aggressive biology. All right, those are great
pearls ready for a quick board blitz.

(20:32):
Let's see how well we've connected the dots with just a
few questions to solidify those key takeaways.
Let's do it. OK, Question one, which imaging
sequence is most critical for defining the gross tumor volume
in a non enhancing WHO grade 2 glioma?
Is it a post operative T1 contrast enhanced MRI, B post
operative T2 flare MRI, C pre operative CT or D diffusion

(20:55):
weighted MRI? OK, think about that cardinal
rule. If you thought B post operative
T2 flare MRI, you're spot on. For these non enhancing tumors,
the entire T2 and Heller hyperintense signal represents
the gross tumor. Perfect question 2.
What is the widely accepted standard isotropic expansion
from the GTV to create the CTV and modern IMRT?

(21:16):
Planning for low grade gliomas? 0.5 centimeters, B 1.0cm, C
1.5cm or D 2.0 centimeters. Right standard margin.
The answer is C 1.5 centimeters.This is the widely accepted
standard really based on those landmark trials for modern IMRT
planning in these cases. Question three.
What is the maximum recommended radiation dose in Gray for low

(21:38):
grade gliomas based on those definitive dose escalation
trials? A 50.4 Gray, B60 Gray, C45 Gray,
or D66 Gray. Tricky phrasing maybe, with 50.4
and 54 often discussed, but the trials established the lack of
benefit above 54 Gray. The common prescription is 50.4
to 54 Gray. Given the options, the best

(21:59):
answer reflecting the trial conclusions on maximum
recommended to dose before toxicity increases without
benefit points towards the lowerend established as sufficient.
So a 50.4 Gray is often cited asthe standard target, with up to
54 being the upper limit before diminishing returns.
Let's stick with A is reflectingthe core finding against higher
doses. Good clarification, OK.
And our final question number 4A, patient's grade 2

(22:20):
astrocytoma is found to have a homozygous deletion of the CDK,
KN 2A and B gene according to the 2021 WHO classification.
How does this change the diagnosis?
A it remains a grade 2 astrocytoma but is considered
high risk. B, it is upgraded to a grade 3
astrocytoma. C it is automatically upgraded
to an astrocytoma IDH mutant WHOgrade 4 or D it is reclassified

(22:43):
as an oligodendroglioma. And the answer here highlighting
that huge molecular impact is C It is automatically upgraded to
an astrocytoma IDH mutant WHO grade 4.
This is just a critical molecular finding per the 2021
WHO classification that fundamentally alters prognosis
and treatment approach. Yeah.
And these molecular updates bring us perfectly actually to a

(23:06):
quick discussion on controversies and advances,
particularly the significant impact of the 2021 WKGO
classification changes on gliomagrading overall.
As we just saw with that last question, molecular markers like
the CDK and 2A and B homozygous deletion can fundamentally
reclassify a tumor that looks low grade under the microscope,
pushing it into a much more aggressive treatment paradigm.

(23:27):
This is really a profound shift in how we practice neuro
oncology day-to-day. Absolutely.
And along with these classification changes, we've
also seen that evolving landscape of chemotherapy
choices, particularly for the IDH mutant astrocytomas.
We highlighted the practical shift really from the older PCV
regimen towards TMZ. That's largely driven by trial

(23:47):
data like Catanon, which showed,you know, comparable efficacy
but with a much, much better toxicity profile for patients.
It's always about finding treatments that are both
effective and tolerable, especially for these patients
who might live for many years. So.
To sort of summarize our sessiontoday, we really dove deep into
the complexities of low grade glioma management, hopefully

(24:08):
setting you up for the foundational knowledge and those
practical insights you really need.
Yeah, we covered the meticulous planning workshop, really
emphasizing defining the target volume for a Grade 2 glioma as
that T2 and flare abnormality, plus that precise 1.5cm margin
for the CTV typically treated to54 Gray Max.
And we didn't just stop at planning, we reviewed those

(24:30):
absolute crucial OA, AR constraints, the brain stem,
optics, cochlea lens, and the vital importance of patient
counseling on toxicities, especially those long term
neurocognitive effects that are so important for these young
patients. Right.
And finally, our case reviews I think truly helped solidify
understanding of managing the different scenarios, the low
risk, the high risk and especially those molecularly

(24:53):
upgraded gliomas. It helps you think through those
real world decision points. It's truly a dynamic and rapidly
evolving field. It certainly is now.
To continue your board preparation, be sure to complete
practice oral boards over at radongsmartlearn.com.
And please subscribe to Radong Smart Review for our next
comprehensive session. Thanks so much for tuning in.