00:01
So we've made a diagnosis.
00:02
The patient presented,
we did some imaging,
we worked with the histology
and genetic findings
to establish a diagnosis.
00:09
How do we treat these gliomas?
And how do we treat the most
aggressive grade IV glioblastoma?
Well, first patients have
to recover after surgery.
00:18
And typically patients are given
about four to six weeks
for the incision to heal,
and to recover function.
00:24
We want patients to be as strong
before treatment as they can be,
so that they can get through
treatment as functional as possible.
00:32
After that four to six week
recovery,
most treatment regimens
include some type of radiation,
and we'll talk about radiation.
00:39
This is followed by a few week
or four week recovery,
and then that's followed by
chemotherapy.
00:44
There are three types
of chemotherapy.
00:46
Neoadjuvant chemotherapy is
given prior to definitive treatment,
which we don't tend
to see or use with gliomas.
00:54
Concurrent chemotherapy
is given at the same time
as definitive treatment
along with radiation.
00:59
And then adjuvant chemotherapy
is given after definitive treatment.
01:03
And here we see
typically for gliomas
that's given after
radiation therapy.
01:07
So this is how
we're going to treat patients.
01:10
Let's dive into each one
of these modalities
and understand more,
how we use those and
what patients experience?
First, let's think about,
how patients do?
A long time ago, the only treatment
we had for gliomas was surgery.
01:24
And with no treatment
or surgery alone,
outcomes are extremely poor
from high grade gliomas,
typically grade IV gliomas
with a median survival
of only around four months.
01:35
These are the most aggressive
of the brain tumors we will cover
and can be very
unresponsive to treatment,
and even difficult
without treatment.
01:44
Over time, radiation was added
to our toolbox of treatments,
and we saw an improvement
in survival to nine months.
01:51
We got smarter about
how much radiation to give?
And currently give about 60 gray.
That's how we dose radiation.
01:57
And that's a treatment dose of
radiation for a brain tumor,
with a median survival
of around 12 months.
02:04
Over time, in decades ago,
our field added
certain types of chemotherapy,
or wafers into the tumor, and some
minimal gains in median survival
until the addition of
a chemotherapy
that we'll talk a little more about
in a minute called temozolomide,
with a median survival
of around 15 months.
02:21
The more coordinated our care is
the better patients do.
02:24
And ultimately, the last treatment
to be added to the regimen
for patients with gliomas
is called Tumor Treatment Fields.
02:30
And currently, the median survival
for glioblastoma is around
20 to 24 months for around
two years from diagnosis.
02:37
These are tough tumors
that require
a comprehensive
and multidisciplinary group
and need to be treated
at an experienced center.
02:46
So how do we think about
each of these treatments?
Well, let's start first
with surgery.
02:50
And I like to think about surgery
in two ways.
02:53
They're surgery
that take out golf balls,
and they're surgery
that scoop up sand.
02:58
And that's really the two types of
tumors that we see on the brain.
03:01
Our grade I tumors
are like those golf balls.
03:04
They're well circumscribed tumors
that do not infiltrate the brain,
they displace the brain,
and can be plucked out with surgery.
03:12
Those are tumors that with a maximal
surgery, or gross total resection,
can be surgically cured
without any adjuvant therapy,
any additional treatment needed
after surgery.
03:23
And that's the example
of our grade I gliomas.
03:26
Grade II, III, and IV
gliomas are infiltrating tumors.
03:30
They're much more like this sand
dropped on a patch of grass.
03:34
You can see
where most of the sand is
and the surgeon can take that out
with surgery,
but there are granules of sand
that you cannot see on the MRI,
that the surgeon
cannot take out with surgery,
and they will need additional
treatment after surgery.
03:48
So surgery is critical,
as the backbone of
diagnosis and management,
but it's
ineffective and eradicating,
particularly the
infiltrating lesions.
03:57
What's the goal of surgery?
Well, we really have two goals.
04:01
One is to acquire tissue
and make a diagnosis.
04:04
And the other is to remove tumor,
and to cytoreduce
or decrease the
amount of tumor volume
that is needed
for subsequent treatment.
04:12
Acquiring tissue allows
for diagnosis.
04:14
It allows for additional
prognostication
through the genetic testing,
and may provide information
on selecting specific therapies
to target certain genetic events
in tumors.
04:24
Cytoreduction is critical
for removing tumor
and decreasing the
total amount of volume
that will need to be treated
after surgery.
04:33
What about
radiation and chemotherapy?
What's the role for those treatments
after surgery?
Radiation therapy works
for the vast majority of tumors.
04:41
This is the backbone
of therapy for gliomas.
04:45
And I like to think of radiation
like Pringles,
once you pop,
you can't stop.
04:50
Everybody loves to Pringle,
and all of these tumors
need radiation therapy.
04:54
It is the backbone of treatment,
that the vast majority of tumors
will respond well too.
05:00
Chemotherapy is
a little bit different.
05:02
Only a minority of tumors will
respond to most chemotherapy,
but those that respond
will have an exquisite response.
05:10
I like to think of chemotherapy,
like hot sauce.
05:13
Not everybody likes it,
but those that like it
just dump it on.
05:17
And the same is true for chemo.
05:19
We treat many tumors
with chemotherapy,
knowing that a
minority will respond
and those that do, often will
have a dramatic response.
05:28
So let's think about how we stage in
radiation and chemotherapy
for the treatment of gliomas.
05:33
And we'll start with radiation.
05:35
We've talked in another lecture
about the types
of radiation therapy.
05:38
We talked about
stereotactic radiosurgery,
partial brain radiation,
and whole brain radiation.
05:45
And typically the radiation that's
given for a glioma is that middle,
the partial brain radiation.
05:50
where we want a high dose
delivered to the tumor,
and also good treatment dose
delivered to the margin
where there may be tumor
that we cannot see
underneath the surface.
06:00
There are many types
of chemotherapy regimens,
and there's only two
that I want you to know of.
06:05
One type of chemotherapy
is temozolomide.
06:07
And we'll talk more about that
in the next slide.
06:09
The other is a
combination regimen called PCV.
06:13
And we combine these
chemotherapies to radiation
to help them work better.
06:18
For oligodendrogliomas,
one of the regimens that you may see
is the combination of radiation,
followed after the end of radiation
by this combination regimen, PCV,
which we'll talk about in a minute.
06:29
For astrocytomas, typically,
we would start again with radiation
and after the completion
of radiation,
treat patients with temozolomide
based chemotherapy.
06:38
And for glioblastoma,
we put those things together.
06:41
So patients receive radiation
with concurrent temozolomide,
that means chemotherapy
at the same time as the radiation,
and then after that's completed
chemotherapy alone.
06:51
You don't need to know
each of the individual regimens,
but want to get
some understanding
as to how these treatments are
combined for certain diagnoses,
and certain patients.
07:01
So let's learn a little bit about
two of the most common
chemotherapy regimens for gliomas.
07:06
The first is temozolomide.
It's abbreviated, commonly TMZ.
07:11
It's an oral agent, it's a pill,
and it's an alkylating agent.
07:15
It goes and intercalates DNA.
07:18
Side effects to consider,
and side effects are important
testable questions for board exams
are nausea and myelosuppression.
07:25
And those are the things
that we think about
with many alkylating therapies.
07:30
In addition,
alkylating agents
have a potential risk
long term of causing cancer,
and typically,
that would be leukemia.
07:37
And those are the three side effects
that I'd be thinking about
in a patient or a test question
pertaining to temozolomide.
07:44
How about PCV?
What is that?
It's a combination
chemotherapy regimen
that consists of three medicines:
Procarbazine, CCNU,
and Vincristine.
07:55
And the other name for CCNU
is Lomustine.
07:58
There are three chemotherapies.
08:00
Two of them are oral pills:
The procarbazine and CCNU.
08:04
And one of them is an infusion
or an injection, vincristine.
08:08
We think about
a number of side effects.
08:10
Nausea and myelosuppression
is seen with the two pills,
procarbazine and CCNU,
because those are alkylating agents
and that's the same thing
we saw with temozolomide.
08:19
Neuropathy is seen with vincristine
and is very important to monitor
because once the neuropathy
develops, it cannot be reversed.
08:27
And then two interesting
side effects
are pulmonary fibrosis,
which we can see with CCNU,
and is a buzzword that can show up
with that CCNU chemotherapy
and also the risk of
secondary malignancy.
08:39
So many chemo therapies are used
throughout cancer.
08:41
These are two that are
important to understand
as we think about gliomas.