July 13, 2025 • 15 mins
This is Episode 7: Low-Grade Glioma Part 2: Evidence for Chemo, Dose, and IDH Inhibitors.In our last episode, we established the framework for managing Grade II gliomas, answering the crucial question of when to treat. Today, we address the next logical question: for those high-risk patients we decide to treat, how do we treat them? We will dissect the pivotal evidence that transformed our approach from radiation alone to combined-modality therapy, justify our standard radiation dose by looking at the specific data from the negative dose-escalation trials, and look to the future with the exciting new data on targeted IDH inhibitors.
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:00):
Welcome back to the Radon Smart Reviews CNS Cancer series.
Great to be back. Today we're jumping straight
into a really critical question in CNS oncology.
For those high risk grade 2 glioma patients, the ones who
need treatment right away, what's the best way we should be
treating them? What's the evidence say?
Exactly. Yeah.
(00:20):
Our goal today is to really zeroin on the key studies that
honestly completely changed how we manage these cases.
OK, we'll talk about why we use the standard radiation dose we
do, why just cranking up the dose isn't the answer, and then
get into some really exciting newer data on targeted drugs.
Sounds good, a focus session good for residents at all
(00:41):
levels. That's the plan.
Essential stuff. OK.
So to really get us thinking clinically, let's start with a
case, pretty typical scenario. You'll definitely see OK imagine
a 48 year old executive comes into your clinic, had surgery,
but it was a subtotal resection of a 5 centimeter grade 2
astrocytoma and they've decided yes let's do immediate post
(01:02):
operative therapy. Right, a common situation.
So the question for you, for thelistener is for this patient,
what do we recommend, what's theevidence based move?
And that's the core question, isn't it?
We need the most effective plan backed by solid data.
And this patient, he clearly falls into that high risk
bucket, right? How do we define high risk again
in this context? Yeah, good point.
(01:24):
For these Grade 2 gliomas, high risk essentially means age 40 or
older or having a subtotal resection.
And our guy here, he's 48 and had a subtotal resection.
So definitely high risk. So for years and years, the
standard for these high risk patients was just radiation
therapy alone. That was it.
That was the standard. But then a really major study
(01:46):
came out and just completely shifted things.
Yeah, you're talking about RTOG 9802, Radiation Therapy Oncology
Group. That was the one phase three
trial that really shook things up.
Tell us about it. What do they do?
So they took just over 250 high risk patients like our case and
they randomized them. One group got radiation therapy
(02:06):
alone, the standard 54 grey. The other group got the same 54
grey, but then they followed it up with six cycles of adjuvant
PCV chemotherapy. That's procarbazine, lomestine
and vincristine, right? PCV and the results when they
came out. Pretty dramatic, weren't they?
Oh, stunning. Yeah.
Published in the New England Journal back in 2016, adding
(02:29):
that PCV chemotherapy, it led toa just a massive overall
survival benefit. How massive are we talking?
Well, median overall survival went from 7.8 years with just
radiation OK to 13.3 years with the chemo radiation combo.
Wow, that's that's almost doubled.
It's huge. And look at the 10 year overall
(02:49):
survival rates jump from 40% to 60%.
Incredible and progression free survival.
Also dramatically better went from four years median PFS to
10.4 years. So I mean, this really provided
that level 1 evidence, didn't it?
Absolutely unequivocal level 1 evidence that combined modality
therapy radiation plus chemo wassignificantly better for these
(03:10):
high risk low grade gliomas. It just fundamentally changed
our standard of care. OK, so RTOG 9802 establishes
combined therapy radiation plus PCV is the way to go for high
risk. So the next logical thought is,
well if radiation is good, maybemore radiation is even better.
Did we need to push that dose higher than 54 Gray?
(03:32):
It's a natural question to ask. Seems intuitive, right?
More dose, better kill. But two really important trials
basically answered that with a pretty definitive no.
OK, what were they? First one was from Europe, the
EORTC, European Organization forResearch and Treatment of Cancer
trial 22844, sometimes called the Believers trial.
(03:54):
They took about 350 patients, randomized them to either 45
Gray or a higher dose 59.4 Gray.What did they find?
Well after about six years follow up the five year overall
survival exactly the same 59% ofboth arms.
No difference at. All no benefit to higher dose.
None. OK, that's one strong piece of
evidence. That was the.
(04:14):
Other trial that came from the NCCTG, the Canadian group
initially trial 867251 smaller trial, about 200 patients.
They compared 50.4 grey versus areally quite high dose 64.8
grey. And the result there, Same
story. Pretty much, yeah.
Again, no improvement in survival of the higher dose.
(04:35):
Actually the five year survival was numerically a bit worse in
the high dose arm, though not statistically significant, 64%
versus 72. Percent worse.
OK, but the real issue with the higher dose wasn't just lack of
benefit, it was toxicity. Exactly.
That's the kicker. In that NCCTG trial, the higher
dose literally doubled the rate of severe grade 3 to 5 radiation
(04:58):
necrosis. Yeah, went from about 2 1/2% up
to 5%. So you put those two trials
together, EOR TC-22844 and NCCTG867251, and the message is
crystal clear. Pushing the dose beyond 54 grade
doesn't help patients live longer, and it definitely
increases the risk of serious side effects.
And that's why our standard doseis what it.
(05:20):
Is precisely 50.4 to 54 Gray. That's the sweet spot.
Effective dose minimizes unnecessary toxicity.
OK. So we've got combined therapy is
standard and we know the optimalradiation dose, but you
mentioned PCV chemotherapy earlier and obviously
temazolamide, TMZ is another common chemo pill use for brain
tumors. Very common.
(05:42):
And patients often worry about radiations long term effects,
right? So the question comes up, could
we maybe skip the radiation entirely and just use chemo like
TMZ alone? Yeah, it's a very reasonable
question and one patients ask a lot.
So was there a trial that lookedat that?
There was EORTC again trial 22O33 this one took almost 500
(06:04):
high risk patients, randomized them to either radiation alone
50.4 Grey or Dostens temazolamide.
TMZ, monotherapy, Just the pills.
And what did the overall trial show?
Was TMZ just as good? Well, overall, looking at
everyone in the trial, there wasn't a statistically
significant difference in progression free survival.
(06:24):
Median PFS was 46 months with radiation versus 39 months with
TMZ alone. So maybe TMZ alone is an option.
Then. But here's where you have to dig
a little deeper. The subgroup analysis is
absolutely critical. Here tell me more what subgroup?
They looked specifically at the patients with IDH mutant non
(06:45):
codelated gliomas. Which are basically the
astrocytomas like our case patients.
Exactly your typical grade to astrocytoma.
And in that specific group the results were very different.
How so? Radiation alone was
significantly better for progression free survival.
At five years, the PFS rate was 43% with radiation, compared to
only 19% for those who just got the TMZ monotherapy.
(07:08):
Wow. That's a big difference, yeah.
Less than half is effective. It is.
So this trial, especially that subgroup analysis really kind of
shut the door on using TMZ monotherapy as an upfront
alternative to radiation for these grade 2 IDH mutant
astrocytoma patients. Radiation remains superior in
that setting if you're choosing between those 2 alone.
OK, that clarifies the chemo only question.
(07:30):
Now let's talk about the really new stuff, the cutting edge
targeted therapies. Yeah, this is probably the most
exciting area right now. We're finally seeing drugs that
go after the specific molecular drivers of these.
Tumors. And the big one here is
targeting the IDH mutation, right isocitrate dehydrogenase?
Exactly that mutation is really common in these Grade 2 gliomas,
(07:52):
and the landmark trial here is called the INDIGO trial.
Indigo. OK, what did Indigo look at?
So this was a phase three trial,but it looked at a slightly
different patient population. These were patients with grade 2
ADH mutant gliomas that were either residual after surgery or
had recurred later on. And crucially, these are
patients who had initially been managed with a watch and wait
approach after surgery, so no immediate chemo or radiation.
(08:15):
Gotcha. So surveillance patients whose
tumors started growing again, what did they get?
They were randomized to either get a new oral IDH inhibitor
drug called voricitinib. Vorvicitinib.
Or a placebo. So it's comparing this targeted
drug against just continued observation or placebo?
And the results, published just recently, were pretty
spectacular, weren't they? Oh, absolute practice.
(08:37):
Changing voricitinib massively delayed the time until the
patient needed their next treatment, like radiation or
chemo. How much of A delay are we
talking about? Huge.
Median progression free survival, basically time until
the tumor grew or the patient needed that next therapy was
27.7 months with voracitinib. 27.7 months OK compared to
(08:58):
placebo. Just 11.1 months.
Wow. More than double and the hazard
ratio, I remember that being impressive.
Phenomenal hazard ratio for progression or death was 0.39.
0.39 So maybe explain that quickly that means.
Yeah, it means about a 61% reduction in the risk of the
disease progressing or death forpatients taking voracitinib
(09:18):
compared to placebo. It's a really strong effect.
That's incredible, the first really successful targeted
therapy for this disease. It really is.
It's a huge step forward. Now it's important to be clear,
right? Indigo doesn't suddenly replace
radiation plus PCV for the high risk patient needing initial
treatment like our case. Right, different setting.
Different setting, but for thosepatients with recurrent or
(09:39):
progressive IDH mutant grade 2 glioma, especially after
surveillance, vorositinib is a powerful, exciting new tool we
now have. OK, fantastic overview of the
evidence. Let's try and to lock this all
in now with our clinical pearls,the absolute key takeaways.
All right, Pearl number one, foryour high risk grade 2 gliomas,
adding adjuvant PCV chemo to radiation is the standard.
(10:02):
RTOG 9802 proved it improves median overall survival
dramatically, 7.8 to 13.3 years.That's the benchmark.
Pearl #2 stick to the standard radiation dose 60 to 54 Gray.
Don't escalate higher. EOR TC-22844 and NCC TG867251
(10:24):
showed no benefit and more toxicity with higher doses.
Less is more here. Pearl #3 for the high risk IDH
mutant astrocytomas specifically.
Remember, radiation therapy beats temazolamide monotherapy
that EOR TC22O33 subgroup analysis is key.
Radiation gives better progression free survival in
that specific group. And Pearl #4, the new kid on the
(10:46):
block, The IDH inhibitor voresight nib is highly
effective for progressive or recurrent IDH mutant grade 2
gliomas. Based on the INDIGO trial
significantly improves PFS with that great hazard ratio of 0.39,
a major advance. Yeah, So you put all that
together and the evidence reallystacks up.
Combined modality therapy, radiation plus chemo, either a
(11:07):
PCV or TMZ based on other factors we haven't dug into
today, is the standard for high risk grade 2 gliomas needing
upfront treatment Better than radiation alone?
Better than chemo alone? Excellent, Ready to test these
principles of the quick board blitz?
Let's do it. OK Case 145 year old patient
subtotal resection of a grade 2 astrocycles glitoma deciding on
adjuvant therapy. Which of these has the highest
(11:29):
level evidence for improving overall survival in this high
risk patient? A rads for 54 Gray alone.
B Ras to 64.8 Gray alone. C Ras to 54 Gray followed by PCV
chemo or DTMZ monotherapy. OK, thinking through it, high
risk patient age and subtotal resection, we need overall
(11:50):
survival benefit that points directly to.
C Right radiation to 54 Gray followed by PCV.
That's straight from RTOG 9802. The only one of these options
proven to significantly boost overall survival in this group.
Exactly, high dose is out. TMZ alone isn't superior for
survival. Grads alone is inferior to
combined therapy. Got to be C.
All right, Case 2, patient has agrade 2 glioma, asks you why
(12:12):
you're recommending 54 Gray and not a higher, maybe more
aggressive dose. Your answer is based on which
trials? ARTO G9802 and EOR TC-22845-B,
EOR TC-22844 and NCCTG 867251, CCATNON and Indigo or DNOA dash
(12:34):
O4 and EOR TC22O33. OK, this is about dose
escalation. Which trials showed higher dose
wasn't better and was more toxicThat would be.
E is correct, EOR TC-22844 and NCC TG867251.
Those are the two key dose escalation trials that
definitively put that question to rest for low grade glioma.
Yep, got to know those two for the dose question.
(12:54):
OK last one case 3 42 year old man subtotally resected great to
astrocytoma. He's worried about radiation
side effects. Wants to know if he can just
take chemo pills instead for hisspecific tumor type.
You tell him ATMZ alone is not inferior to radiation.
BPCV alone is superior to radiation C.
(13:14):
Radiation alone is superior to TMZ alone or D Indigo showed
Vorcydnub is the new standard here.
Right, so grade 2 astrocytoma wants chemo instead of
radiation. We talked about this EOR TC-2 to
A33 subgroup analysis. Exactly.
So the answer is C for his specific tumor type.
IDH mutant astrocytoma radiationalone was shown to be superior
(13:36):
to TMZ monotherapy in terms of progression free survival in
that key subgroup analysis. Right, TMZ alone is it non
inferior. PCV alone wasn't tested that way
in a head to head and indigo while great is for a different
setting not upfront treatment comparison like this.
So C is the best answer based onevidence.
Fantastic. That really helps solidify
things. So wrapping up, we've really
covered the essential evidence for managing these high risk,
(13:57):
low grade gliomas today. Yeah, we really established why
combined modality therapy, specifically radiation plus PCV
is the standard based on that huge overall survival win from
RTOG 9802. And we justified why 50 to 54
grey is our go to radiation doseremembering those negative dose
escalation trials EOR TC-22844 and NCC TG867251 no benefit,
(14:24):
more harm above that. And we also saw why chemo
monotherapy isn't the preferred upfront route for actor Cytomas,
thanks to EOR TC-22033 showing radiation superiority over TMZ
alone in that group. And finally looked ahead with
the really exciting results for vorsitinib from Indigo, offering
a new targeted option for progressive or recurrent
(14:44):
disease. It's a rapidly evolving field.
It really is. And you know, thinking about it,
the progress even just in the last decade covered by these
trials is pretty remarkable, from optimizing dose to adding
chemo now to targeted therapy. It really makes you wonder what
the next big step will be, doesn't it?
As you take all this informationforward, just remember how
critical staying updated is if the landscape keeps changing,
(15:06):
and that directly impacts how wecan best help our patients.
Absolutely. Continuous learning is key.
For more practice, including oral board style questions,
definitely check out radonksmartlearn.com.
That's RADONC, smartlearn.com, and make sure you subscribe to
Red on Smart Review for our nextsession.
Thanks so much for tuning in everyone, hope this was helpful.
Welcome back to the Radon Smart Reviews CNS Cancer series.
Great to be back. Today we're jumping straight
into a really critical question in CNS oncology.
For those high risk grade 2 glioma patients, the ones who
need treatment right away, what's the best way we should be
treating them? What's the evidence say?
Exactly. Yeah.
(00:20):
Our goal today is to really zeroin on the key studies that
honestly completely changed how we manage these cases.
OK, we'll talk about why we use the standard radiation dose we
do, why just cranking up the dose isn't the answer, and then
get into some really exciting newer data on targeted drugs.
Sounds good, a focus session good for residents at all
(00:41):
levels. That's the plan.
Essential stuff. OK.
So to really get us thinking clinically, let's start with a
case, pretty typical scenario. You'll definitely see OK imagine
a 48 year old executive comes into your clinic, had surgery,
but it was a subtotal resection of a 5 centimeter grade 2
astrocytoma and they've decided yes let's do immediate post
(01:02):
operative therapy. Right, a common situation.
So the question for you, for thelistener is for this patient,
what do we recommend, what's theevidence based move?
And that's the core question, isn't it?
We need the most effective plan backed by solid data.
And this patient, he clearly falls into that high risk
bucket, right? How do we define high risk again
in this context? Yeah, good point.
(01:24):
For these Grade 2 gliomas, high risk essentially means age 40 or
older or having a subtotal resection.
And our guy here, he's 48 and had a subtotal resection.
So definitely high risk. So for years and years, the
standard for these high risk patients was just radiation
therapy alone. That was it.
That was the standard. But then a really major study
(01:46):
came out and just completely shifted things.
Yeah, you're talking about RTOG 9802, Radiation Therapy Oncology
Group. That was the one phase three
trial that really shook things up.
Tell us about it. What do they do?
So they took just over 250 high risk patients like our case and
they randomized them. One group got radiation therapy
(02:06):
alone, the standard 54 grey. The other group got the same 54
grey, but then they followed it up with six cycles of adjuvant
PCV chemotherapy. That's procarbazine, lomestine
and vincristine, right? PCV and the results when they
came out. Pretty dramatic, weren't they?
Oh, stunning. Yeah.
Published in the New England Journal back in 2016, adding
(02:29):
that PCV chemotherapy, it led toa just a massive overall
survival benefit. How massive are we talking?
Well, median overall survival went from 7.8 years with just
radiation OK to 13.3 years with the chemo radiation combo.
Wow, that's that's almost doubled.
It's huge. And look at the 10 year overall
(02:49):
survival rates jump from 40% to 60%.
Incredible and progression free survival.
Also dramatically better went from four years median PFS to
10.4 years. So I mean, this really provided
that level 1 evidence, didn't it?
Absolutely unequivocal level 1 evidence that combined modality
therapy radiation plus chemo wassignificantly better for these
(03:10):
high risk low grade gliomas. It just fundamentally changed
our standard of care. OK, so RTOG 9802 establishes
combined therapy radiation plus PCV is the way to go for high
risk. So the next logical thought is,
well if radiation is good, maybemore radiation is even better.
Did we need to push that dose higher than 54 Gray?
(03:32):
It's a natural question to ask. Seems intuitive, right?
More dose, better kill. But two really important trials
basically answered that with a pretty definitive no.
OK, what were they? First one was from Europe, the
EORTC, European Organization forResearch and Treatment of Cancer
trial 22844, sometimes called the Believers trial.
(03:54):
They took about 350 patients, randomized them to either 45
Gray or a higher dose 59.4 Gray.What did they find?
Well after about six years follow up the five year overall
survival exactly the same 59% ofboth arms.
No difference at. All no benefit to higher dose.
None. OK, that's one strong piece of
evidence. That was the.
(04:14):
Other trial that came from the NCCTG, the Canadian group
initially trial 867251 smaller trial, about 200 patients.
They compared 50.4 grey versus areally quite high dose 64.8
grey. And the result there, Same
story. Pretty much, yeah.
Again, no improvement in survival of the higher dose.
(04:35):
Actually the five year survival was numerically a bit worse in
the high dose arm, though not statistically significant, 64%
versus 72. Percent worse.
OK, but the real issue with the higher dose wasn't just lack of
benefit, it was toxicity. Exactly.
That's the kicker. In that NCCTG trial, the higher
dose literally doubled the rate of severe grade 3 to 5 radiation
(04:58):
necrosis. Yeah, went from about 2 1/2% up
to 5%. So you put those two trials
together, EOR TC-22844 and NCCTG867251, and the message is
crystal clear. Pushing the dose beyond 54 grade
doesn't help patients live longer, and it definitely
increases the risk of serious side effects.
And that's why our standard doseis what it.
(05:20):
Is precisely 50.4 to 54 Gray. That's the sweet spot.
Effective dose minimizes unnecessary toxicity.
OK. So we've got combined therapy is
standard and we know the optimalradiation dose, but you
mentioned PCV chemotherapy earlier and obviously
temazolamide, TMZ is another common chemo pill use for brain
tumors. Very common.
(05:42):
And patients often worry about radiations long term effects,
right? So the question comes up, could
we maybe skip the radiation entirely and just use chemo like
TMZ alone? Yeah, it's a very reasonable
question and one patients ask a lot.
So was there a trial that lookedat that?
There was EORTC again trial 22O33 this one took almost 500
(06:04):
high risk patients, randomized them to either radiation alone
50.4 Grey or Dostens temazolamide.
TMZ, monotherapy, Just the pills.
And what did the overall trial show?
Was TMZ just as good? Well, overall, looking at
everyone in the trial, there wasn't a statistically
significant difference in progression free survival.
(06:24):
Median PFS was 46 months with radiation versus 39 months with
TMZ alone. So maybe TMZ alone is an option.
Then. But here's where you have to dig
a little deeper. The subgroup analysis is
absolutely critical. Here tell me more what subgroup?
They looked specifically at the patients with IDH mutant non
(06:45):
codelated gliomas. Which are basically the
astrocytomas like our case patients.
Exactly your typical grade to astrocytoma.
And in that specific group the results were very different.
How so? Radiation alone was
significantly better for progression free survival.
At five years, the PFS rate was 43% with radiation, compared to
only 19% for those who just got the TMZ monotherapy.
(07:08):
Wow. That's a big difference, yeah.
Less than half is effective. It is.
So this trial, especially that subgroup analysis really kind of
shut the door on using TMZ monotherapy as an upfront
alternative to radiation for these grade 2 IDH mutant
astrocytoma patients. Radiation remains superior in
that setting if you're choosing between those 2 alone.
OK, that clarifies the chemo only question.
(07:30):
Now let's talk about the really new stuff, the cutting edge
targeted therapies. Yeah, this is probably the most
exciting area right now. We're finally seeing drugs that
go after the specific molecular drivers of these.
Tumors. And the big one here is
targeting the IDH mutation, right isocitrate dehydrogenase?
Exactly that mutation is really common in these Grade 2 gliomas,
(07:52):
and the landmark trial here is called the INDIGO trial.
Indigo. OK, what did Indigo look at?
So this was a phase three trial,but it looked at a slightly
different patient population. These were patients with grade 2
ADH mutant gliomas that were either residual after surgery or
had recurred later on. And crucially, these are
patients who had initially been managed with a watch and wait
approach after surgery, so no immediate chemo or radiation.
(08:15):
Gotcha. So surveillance patients whose
tumors started growing again, what did they get?
They were randomized to either get a new oral IDH inhibitor
drug called voricitinib. Vorvicitinib.
Or a placebo. So it's comparing this targeted
drug against just continued observation or placebo?
And the results, published just recently, were pretty
spectacular, weren't they? Oh, absolute practice.
(08:37):
Changing voricitinib massively delayed the time until the
patient needed their next treatment, like radiation or
chemo. How much of A delay are we
talking about? Huge.
Median progression free survival, basically time until
the tumor grew or the patient needed that next therapy was
27.7 months with voracitinib. 27.7 months OK compared to
(08:58):
placebo. Just 11.1 months.
Wow. More than double and the hazard
ratio, I remember that being impressive.
Phenomenal hazard ratio for progression or death was 0.39.
0.39 So maybe explain that quickly that means.
Yeah, it means about a 61% reduction in the risk of the
disease progressing or death forpatients taking voracitinib
(09:18):
compared to placebo. It's a really strong effect.
That's incredible, the first really successful targeted
therapy for this disease. It really is.
It's a huge step forward. Now it's important to be clear,
right? Indigo doesn't suddenly replace
radiation plus PCV for the high risk patient needing initial
treatment like our case. Right, different setting.
Different setting, but for thosepatients with recurrent or
(09:39):
progressive IDH mutant grade 2 glioma, especially after
surveillance, vorositinib is a powerful, exciting new tool we
now have. OK, fantastic overview of the
evidence. Let's try and to lock this all
in now with our clinical pearls,the absolute key takeaways.
All right, Pearl number one, foryour high risk grade 2 gliomas,
adding adjuvant PCV chemo to radiation is the standard.
(10:02):
RTOG 9802 proved it improves median overall survival
dramatically, 7.8 to 13.3 years.That's the benchmark.
Pearl #2 stick to the standard radiation dose 60 to 54 Gray.
Don't escalate higher. EOR TC-22844 and NCC TG867251
(10:24):
showed no benefit and more toxicity with higher doses.
Less is more here. Pearl #3 for the high risk IDH
mutant astrocytomas specifically.
Remember, radiation therapy beats temazolamide monotherapy
that EOR TC22O33 subgroup analysis is key.
Radiation gives better progression free survival in
that specific group. And Pearl #4, the new kid on the
(10:46):
block, The IDH inhibitor voresight nib is highly
effective for progressive or recurrent IDH mutant grade 2
gliomas. Based on the INDIGO trial
significantly improves PFS with that great hazard ratio of 0.39,
a major advance. Yeah, So you put all that
together and the evidence reallystacks up.
Combined modality therapy, radiation plus chemo, either a
(11:07):
PCV or TMZ based on other factors we haven't dug into
today, is the standard for high risk grade 2 gliomas needing
upfront treatment Better than radiation alone?
Better than chemo alone? Excellent, Ready to test these
principles of the quick board blitz?
Let's do it. OK Case 145 year old patient
subtotal resection of a grade 2 astrocycles glitoma deciding on
adjuvant therapy. Which of these has the highest
(11:29):
level evidence for improving overall survival in this high
risk patient? A rads for 54 Gray alone.
B Ras to 64.8 Gray alone. C Ras to 54 Gray followed by PCV
chemo or DTMZ monotherapy. OK, thinking through it, high
risk patient age and subtotal resection, we need overall
(11:50):
survival benefit that points directly to.
C Right radiation to 54 Gray followed by PCV.
That's straight from RTOG 9802. The only one of these options
proven to significantly boost overall survival in this group.
Exactly, high dose is out. TMZ alone isn't superior for
survival. Grads alone is inferior to
combined therapy. Got to be C.
All right, Case 2, patient has agrade 2 glioma, asks you why
(12:12):
you're recommending 54 Gray and not a higher, maybe more
aggressive dose. Your answer is based on which
trials? ARTO G9802 and EOR TC-22845-B,
EOR TC-22844 and NCCTG 867251, CCATNON and Indigo or DNOA dash
(12:34):
O4 and EOR TC22O33. OK, this is about dose
escalation. Which trials showed higher dose
wasn't better and was more toxicThat would be.
E is correct, EOR TC-22844 and NCC TG867251.
Those are the two key dose escalation trials that
definitively put that question to rest for low grade glioma.
Yep, got to know those two for the dose question.
(12:54):
OK last one case 3 42 year old man subtotally resected great to
astrocytoma. He's worried about radiation
side effects. Wants to know if he can just
take chemo pills instead for hisspecific tumor type.
You tell him ATMZ alone is not inferior to radiation.
BPCV alone is superior to radiation C.
(13:14):
Radiation alone is superior to TMZ alone or D Indigo showed
Vorcydnub is the new standard here.
Right, so grade 2 astrocytoma wants chemo instead of
radiation. We talked about this EOR TC-2 to
A33 subgroup analysis. Exactly.
So the answer is C for his specific tumor type.
IDH mutant astrocytoma radiationalone was shown to be superior
(13:36):
to TMZ monotherapy in terms of progression free survival in
that key subgroup analysis. Right, TMZ alone is it non
inferior. PCV alone wasn't tested that way
in a head to head and indigo while great is for a different
setting not upfront treatment comparison like this.
So C is the best answer based onevidence.
Fantastic. That really helps solidify
things. So wrapping up, we've really
covered the essential evidence for managing these high risk,
(13:57):
low grade gliomas today. Yeah, we really established why
combined modality therapy, specifically radiation plus PCV
is the standard based on that huge overall survival win from
RTOG 9802. And we justified why 50 to 54
grey is our go to radiation doseremembering those negative dose
escalation trials EOR TC-22844 and NCC TG867251 no benefit,
(14:24):
more harm above that. And we also saw why chemo
monotherapy isn't the preferred upfront route for actor Cytomas,
thanks to EOR TC-22033 showing radiation superiority over TMZ
alone in that group. And finally looked ahead with
the really exciting results for vorsitinib from Indigo, offering
a new targeted option for progressive or recurrent
(14:44):
disease. It's a rapidly evolving field.
It really is. And you know, thinking about it,
the progress even just in the last decade covered by these
trials is pretty remarkable, from optimizing dose to adding
chemo now to targeted therapy. It really makes you wonder what
the next big step will be, doesn't it?
As you take all this informationforward, just remember how
critical staying updated is if the landscape keeps changing,
(15:06):
and that directly impacts how wecan best help our patients.
Absolutely. Continuous learning is key.
For more practice, including oral board style questions,
definitely check out radonksmartlearn.com.
That's RADONC, smartlearn.com, and make sure you subscribe to
Red on Smart Review for our nextsession.
Thanks so much for tuning in everyone, hope this was helpful.
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