Hi, I'm Dr. Beth Helmink, and I'm an assistant professor of
surgical oncology at MD Anderson Cancer Center.
Today I'm joined by Dr. John Paul Shen, who is an assistant
professor of GI Medical Oncology at MD Anderson Cancer
Center. And this is the Cancerwise Podcast.
Welcome, Dr. Shen. Thank you for being here with me today.
Thanks so much for having me.
Absolutely. Today we're going to discuss appendix
cancer, the rates of appendix cancer and how they're going
up in young people. And then talk a little bit about new
research into new treatment options for these patients.
Should we start with an overview of appendix cancer and why
it can be so difficult to treat?
You know, appendix cancer is known as a rare
tumor, but it is becoming more common.
And it's not rare at all at MD Anderson, we see,
you know, between 300 to 400 new patients every year
as a, as an institution.
I personally see generally three new appendix cancer
patients every week.
And appendix cancer has been hard to treat for
a lot of reasons. I think a big part of that is this,
I think now, people recognize, outdated idea that appendix
cancer is the same as colon cancer, and that the patients
get the same chemotherapy as colon cancer,
because we know that at least for some types of appendix
cancer, this colon cancer chemotherapy doesn't work very
well.
And why do you think we're seeing it now more in
young people? So, there was a recent study that came out
saying that we are seeing increasing rates of appendix
cancer being diagnosed, but specifically among younger
people. Do you have any insight into to why that might be?
Yeah. So, great question.
Why questions are always difficult, but I think there's
a lot of reasons to think that it could be related to
potentially diet and to microbiome.
You know, the, the scary part is, is that when the
people who are in their 20s and 30s are now in
their, you know, as they progress into their 50s and 60s,
we expect that the rates are going to be even higher.
And so, you know, it's really critical that we develop
better treatments for appendix cancer because the,
unfortunately, we may be looking at the tip of the iceberg
in terms of the number of, of new patients.
Yeah. What I think was great about this study is they
actually looked at the rates in young people as compared to
older people. It's not that appendix cancer is being
diagnosed as a whole more.
It is. But but also specifically among younger people.
Right? Because you could argue, you know, because there was
confusion, you know, a while back or, you know,
years ago, that it could be just colon cancer, is the same
as colon cancer, right? I think there is now a,
a better diagnosis.
And so, we are diagnosing it globally more frequently.
But to see that increase specifically in younger people
suggests that, you know, we could have a real problem
going forward if this is to continue.
We're seeing also in other colon cancer and other GI
cancers, also increasing rates among younger people.
We both see a lot of appendix cancer.
It's obviously a difficult disease for us to treat because
it's often presents late. Do you have any insight into why
that is, or why it is so difficult
for people to find and to diagnose?
You know, it's unfortunate that the vast majority of
patients with appendix cancer don't have any symptoms
until the tumor is already spread throughout their abdomen,
and that is partially because you can't feel your appendix.
In some cases, the appendix tumor can cause
an appendicitis.
And then you would have pain and you'd go to the emergency
room. In that case, when it is caught
early, the outcomes are very good.
We, our data, as you know, shows that the chance
of being alive five years down the road, if you're caught
at stage II or stage III, is better than 95%.
So, the vast majority of those people are cured.
The problem is, it's very silent in that
if the tumor is not near the very tip of the appendix,
you won't know that you have it until it's already
spread throughout your abdomen, at which point it's
already metastatic.
I think the other thing that's unique from colon cancer
is that, you know, people get colonoscopies and they come
to me so frustrated that their colonoscopy didn't show
anything. But what they don't realize is that, you know, a
colonoscopy is never going to look inside the appendix or
be able to, you know, the scope itself is bigger than the
appendix. And so you can't actually look inside.
So, there's, there's no way to screen for this.
There's no way, and it doesn't cause symptoms.
So, it unfortunately is discovered very late.
I think the other thing is, you know, it is often
misdiagnosed.
So many of our female patients, for example, are
misdiagnosed as ovarian cancer.
And that's partially just because it similarly spreads in
the same way.
And it similarly has vague symptoms that, you know,
and a lot of these tumors actually do form ovarian
metastases too. So, sometimes these people do have ovarian
masses. It's just coming from the appendix, not coming
from the ovary. What do you think makes it so difficult to
treat with regards, I know you alluded to the chemo options
and how it is not colon cancer, but what are the
struggles that you face with treating these patients from a
medical oncology side?
Yes, a great question.
The, you know, the, because
it's a relatively rare tumor, there has not been a lot
of investment in prospective clinical trials,
which is generally, you know, considered to be the gold
standard of, you know, medical knowledge.
And that is generally what, you know, informs
you as an oncologist. These are the treatments that work.
And the other thing that we've been doing a lot in our
research is that we can recognize that
while appendix cancer is a unique entity, it shares
common features with other more common tumors.
And we, we've identified that, you know, there are drugs
that are being developed for other tumor types that are
active in, in appendix cancer.
And one one classic example that we've shown recently is
that, you know, the old drug paclitaxel, which
was not used in appendix cancer because it doesn't work in
colon cancer, but it works in other GI tumors,
in breast cancer. We found, you know, turns out to be quite
active in appendix cancer. And so, we think that there's
going to be many other opportunities to take
drugs that work in other tumors and identify, you know,
the subtypes or the subset of patients where they're
working in appendix cancer.
It sounds like, you know, while there aren't drugs approved
specifically for appendix cancer, number one, there are
treatment options that we can use that are used for other
cancers. And thinking about the unique features of
appendix cancer that are more like other cancers
kind of helps you think about different types of treatments
that may already exist and are used in other cancers.
Is that, is that correct, or how do you approach a new
appendix cancer patient?
Yeah. So that's that's a great question.
So, we don't have drugs specifically for
appendix cancer, but that doesn't mean that we don't treat
our appendix cancer patients. And so, we try to learn
as much about the tumor as possible by doing molecular
testing. We see what genes are mutated in that
tumor. We now have specialized
ways that we can look to see how the immune system and
the non-tumor cells around the tumor are reacting to the
tumor. And based on that, it helps us identify,
you know, potential targeted treatments, the potential
to use immune therapies, which have been very effective in
other tumors and, and in some cases, effective in appendix
cancer versus, you know, the kind of traditional colon
cancer chemotherapy.
I should add, you know, as a surgeon, like obviously
surgery is, is a mainstay of appendix cancer
treatment as well. And, you know, how do you think about
getting patients to surgery or getting patients to see a
surgeon? Like, how do you think about when you see a
patient, when to engage surgery, when not to?
You know, far and away, the best treatment for appendix
cancer is to remove it all surgically.
There is a very good chance that even
though it's metastatic to the abdominal space,
patients can still be cured, which, which is pretty
incredible.
You know, it is a challenging question that we're still
working on who should have a surgery and who not.
You know, part of that is related, as you know, to the
amount of spread of the tumor, but part of it is also
related to how aggressive the tumor is.
And we're, we're trying to get better at predicting, you
know, which tumors are very likely to come back
after surgery versus which tumors are less likely to come
back, and, you know, those are the patients that are really
going to benefit from having the surgery.
Yeah. And to your point about aggression, like, I guess we
should talk too a little bit about the the grades of
appendix cancer, because some, some appendix cancers are
quite low grade, meaning not very aggressive, while
others are very high grade.
And and you know, for the low-grade patients anyway,
surgery in fact is, is one of the best
treatments. And in fact, we often don't treat those
patients with chemotherapy.
So, great, great point. And it really, I should have said
this when you asked the question about, you know, what
makes appendix cancer so hard to treat.
A big part of it is that, you know, appendix cancer is
relatively rare, but it's also very diverse.
And so, because it's not that common, there's always
been a tendency to lump together low-grade tumors,
which, you know, grow very slowly.
Don't respond very well to traditional chemotherapy and are
best treated with surgery. You know, those get lumped
together with high-grade tumors, which are, you know, on
the spectrum more similar to colon cancer, you know,
probably should get chemotherapy.
And it's very unfortunate because we, you know, very
commonly we'll see people, you know, coming to us with
low-grade tumors that have been getting, you know, sick
from chemotherapy that's not really helping that much.
When in reality, they probably could have had a surgery.
Yeah. I mean, I think one of my favorite studies that we've
done here is your study on low-grade appendix cancer,
where you guys literally took patients who had the same
disease and either gave them chemo or not, and then
switched it later on. So the patients that had not gotten
chemo got chemo, and the ones that had gotten
chemo went off of it and basically saw no difference
at all in what that tumor did with chemotherapy.
Yeah, absolutely. Yeah. So, yeah, specifically for
low-grade mucinous appendix cancer, which is a significant
fraction, maybe a third to 40% of all appendix
cancer tumors, you know, don't
really respond very well at all to 5-FU chemotherapy,
which is the backbone of, of colon cancer chemotherapy and
that, you know, that study which was, you know, started
many years ago even before I got to MD Anderson, really
is what, you know, solidified me that we need better
treatments. We can't just keep, you know, using
colon cancer chemotherapy and expecting it to work
for appendix cancer because they're just very different.
Yeah. And the surgery for those different patients
are very different as well.
You know, for low-grade patients we can be quite aggressive
surgically and still have really good outcomes.
I mean, these patients with low-grade tumors we anticipate
will live for years, many years and
for higher-grade patients, you know, we work with you
really closely and try to think about when might be the
best time to operate. You know, we obviously have to be
technically able to resect everything, but we also kind
of talk about whether it biologically makes sense.
You know, if we think we can get them a long time
of not having cancer or not requiring another
treatment, than then it's probably worth it.
So, I'll ask you a question. So, why do you why do you
think it's important for a patient with appendix cancer to
come to a place with surgical expertise?
Yeah, I think it's absolutely the most important thing,
honestly.
I think, you know, you alluded to the fact that we see a
lot of patients who, unfortunately, are treated a little
bit differently than than we would.
I hesitate to say incorrectly because it's not
with malintent. It's just what, you know, because it's a
rare tumor the, the practitioners just aren't familiar with
it, aren't familiar with the latest research and the latest
findings and the latest treatment guidelines.
And so, as you mentioned, we see a number of patients who
have been treated with chemo where it's not been helpful
and it's only causing problems.
We also talked about patients who are misdiagnosed and kind
of mismanaged and being treated with ovarian cancer, for
example. And we see them and clearly, this is coming from
the appendix. And so, I think what we offer here is,
you know, we have excellent pathologists who specialize
in this disease and are able to kind of sort out low-grade
and high-grade. We have radiologists who are very good at
picking out small tumors, which this disease happens to
form. The radiology is not straightforward.
We have medical oncologists who think about this and are
clearly thinking along the lines of, you know, this, this
is a unique cancer. This is not colon cancer.
We need to be thoughtful about this.
And then from a surgery standpoint, you know, it's not just
our surgeons who are specialized, but, you know, my job is
rather unique because I treat only appendix cancer.
No other surgeon in America other than the surgeons
here really, really have that degree of specialization
because they just wouldn't see enough patients.
But we have enough patients here where that is actually the
job of three full-time surgeons here.
The number of surgeries we do here, too, it leads to
specialization in our anesthesiologists, our nursing staff,
our floor staff. Around the time of your surgery,
you know, you're cared for by people who see these patients
all the time, rather than going to a center who does maybe
two or three of these a year.
You know, we do over 70 of these a year.
So, I think for all of those reasons.
And then I think, you know, the other thing for us is, is
our multidisciplinary conferences that we have every week,
which, you know, we have every Tuesday
morning, basically. And, you know, we combine a group
of probably 15 to 20 physicians sometimes
on the call, who are thinking about a given patient
from all of these different perspectives, and all of these
people on the call have specific expertise in appendix
cancer. I think it makes complete sense.
You and I are working on a phase I study together.
And this is something I'm really excited about.
But this, you know, is a result of
the work that your group had done regarding the use
of paclitaxel, which you alluded to earlier, a drug that,
you know, kind of had not been used in appendix cancer
previously. But can you talk about how you figured out how
that it might be a good target in patients with appendix
cancer?
Yeah, absolutely. No, I, I share your excitement.
Paclitaxel is a well known chemotherapy
drug. It's been used to treat literally hundreds of
thousands, if not millions of women with breast cancer.
And it's active in esophagus cancer and gastric
cancer.
Really, colon cancer is kind of the exception where it
doesn't work very well in colon cancer.
But we thought that because
of the mutation profile of appendix cancer being different
than colon cancer, we thought, you know, paclitaxel
in that class of drugs called taxanes would be active.
So, as a way to test this, we, you know, made
preclinical models which which took a lot of work so that
we would have ways to kind of test our ideas before moving
into patients. But it worked very well there.
And then based on that success, we were able to open
the clinical trial, which do you want to talk about how
it's going?
Yeah, I mean, I think it's going really well.
You know, it uses paclitaxel.
It's in patients that we are not able to operate
on. So, so typically, patients with high-grade disease
who don't really have a lot of other options.
And so, you know, basically that
trial requires a diagnostic laparoscopy
or a surgery at the beginning to look at the disease,
see where it is, what it looks like, and at the same
time we place a port. So, just like a port that goes in
your vein for IV chemotherapy, this one just goes
into your abdomen.
And we actually deliver the chemo right into the abdomen.
This is not a new concept altogether.
This, this has been used in patients with gastric cancer
and ovarian cancer kind of over many years.
And actually, there are phase III clinical trials or lots
of patients that have been treated. And it's actually been
shown to be beneficial in those cancers.
And so, this is the only time that it has been used
in appendix cancer, though, and I think that's what makes
this unique. But we place the port.
And then over the course of eight weeks, we deliver
chemotherapy directly into the abdomen.
Thus far, we've treated about 12 patients now.
And you know, we had to lower the dose once, but that's
it. And this dose has been very well tolerated.
And in fact, we're actually seeing some pretty impressive
results. You know as well as I do that it's kind of hard
to determine the amount of cancer by a scan.
So, we're using scans.
We're using tumor markers.
We're using that the diagnostic
laparoscopy also to kind of see how the disease is
responding. But I will say we've had multiple patients
who've who've had really good results.
Yeah, I, I share your excitement.
This is, we think, going to be a launching pad
for combinations.
You know, pretty much every curative or highly
effective regimen in cancer uses not just one
drug but multiple drugs.
I'm an impatient person by nature, but you know,
the way that you have to go about is you have to do one
drug first and show that that works.
And essentially that is nearly done.
And so, now we're really excited for and are already
planning for combination studies, where will combine
paclitaxel with drugs that activate the immune
system to try to get a synergistic effect.
Yeah. But but to have seen, you know, results
with just the single drug, like you said, to
me, is really impressive. And I would also add that these
are patients who, you know, multiple lines of chemotherapy
have not worked really well on.
And so, you know, despite that, these patients are still
seem to be having a response to this particular drug.
So, you know, in addition to the combinations of
different agents, gosh, it might be nice to move this
earlier into their treatment regimen
so that we could catch them at a little bit earlier stage
when they have less disease. And it might be even more
beneficial in those patients.
Yeah, absolutely.
We we may even be able to, you
know, achieve shrinking the tumor enough to potentially get
patients who weren't previously candidates for surgery to
surgery if we can move it up into an earlier
line of therapy, which, which is something that we were
actively attempting
to do.
Yeah, I think it's it's great.
And as you said, gosh, it's it's not the answer for
sure, but it's at least a baby step towards getting there.
And as you said, this is just a process.
And if we don't start though somewhere we're we're not
going to get anywhere is kind of how I look at it.
Before we wrap up, we should maybe talk about some of the
difficulties that patients experience while being treated
with this. You know, whether they are being misdiagnosed
or, you know, they don't feel like they're getting anywhere
with their diagnosis or they have a diagnosis that's
confusing to them, but they think they may have appendix
cancer or patients with appendix cancer who feel like
they've kind of reached the extent of what their local
oncologist knows about appendix cancer.
Like, how do you recommend that those patients, you know,
advocate for themselves or advocate for their own family
members who might be suffering from from this disease?
Yeah. Great question. I think it's important, you know, as
a patient, you do need to advocate for yourself.
And if you don't, you
know, feel like the plan that you're on is making sense.
It's important to ask questions.
And your oncologist should not feel threatened.
If you ask, you want, you know, a second opinion, someone
that has more experience.
You know, we actually have a really good relationship with
medical oncologists because people will come to us, we'll
give chemotherapy recommendations, and they'll go back
close to home and they'll, and they'll, you know, continue
the therapy close to home. From a medical oncology
standpoint, you know, rather than trying to figure out how
to treat a rare disease on your own, they would rather
you go and see a specialist, come up a the treatment plan,
bring that back home, and then you can continue
your infusions locally.
And from a surgery standpoint, well, gosh, I say the same
thing, right? I, as a surgeon, I would never be offended
if one of my patients asked to get a second opinion.
Right? And I think with these surgeries being such
a big undertaking for the patient, I think it's totally
appropriate that they, you know, even if a surgeon on the
outside is saying they need this particular surgery,
they need the the appendix cancer surgery,
that they ask for a second opinion.
And I also, you know, have a cohort of my own patients
who are always very willing and
able to talk to other patients you know, about to undergo
the surgery or about, you know, or just have
received this diagnosis.
And gosh, I think it's so helpful for them to talk to other
patients who have been through something similar again,
just since it's such a rare disease.
What are common questions that patients ask you about
the cytoreductive surgery for appendix cancer?
Yeah, I mean, I think the surgery
itself is a pretty big surgery.
And so, you know, we talked a little bit about appendix
cancer, why it's so hard to treat.
And part of the reason surgically why it's so hard to treat
is it actually forms lots of tiny little tumors
in lots of different places in the abdomen.
When we do this surgery, it could mean anything
from, you know, a colon resection to
a small bowel resection to part of the stomach, the
gallbladder, the spleen, the omentum, the ovaries, the
uterus.
You know, it can really be, you know, a kind of 15
different surgeries combined into one.
And that, you know, it just is a very
hard surgery to undergo because of all those,
you know, all the little complications that can arise from
any one of those surgeries just gets combined.
The other thing that we do for this disease, to address all
those tiny little things we may not be able to see and may
not be able to get out.
We do something called heated intraperitoneal chemotherapy
or HIPEC. So, you know, what that is
is basically pouring heated chemo
into the abdominal cavity and circulating that through over
the course of about an hour, hour and a half.
Again, the goal of that is to address all those little
things that we can't take out.
But you know that chemo has effects
and it has effects on healing.
It has effects on the bowel and how the bowel recovers
after a big surgery. And so all of this together, you
know, it just means that this is a very long recovery for
patients. And so, I mean, honestly, you know, I usually
tell patients to expect to be in the hospital at least a
week, probably closer to ten days.
You know, they often have not been able to eat or drink
regular food for about a week.
Sometimes we even have to use IV nutrition.
I usually tell patients that even when they go home,
they're not going to be back to normal, and they may not
get back to normal for about six or nine months, to be
honest. Where they, you know, are having no pain or no
problems with eating or have normal energy levels.
Now, that doesn't mean that we don't get people through
this routinely like we do a lot of these surgeries and many
patients do quite well, but it certainly has
the potential for a very long recovery.
And so, I think patients kind of come in knowing a little
bit about this and kind of having read a little bit about
it. And so, their questions are usually along the lines of,
you know, is it really this bad?
And, you know, I think, as you said earlier, like
coming to a place where we do this all the time and coming
to a place where the surgeons are very experienced in this,
and there are multiple surgeons here who do it, you know,
gives them the best shot at having a really good outcome.
But, you know, mostly I have to allay their fears that
this is something we get people through every week here
and every day here.
And it's, it's definitely doable, but it is something
that we do have to think long and hard about and be very
thoughtful about when and who we operate on.
But I think most times when patients come to me, they're,
they're scared about the surgery.
And I think my job is to educate.
Well thank you, JP. This was, this was fantastic.
This was a really great conversation, and I think really
helpful discussion of appendix cancer.
Yeah. Thank you so much for having me.
This was a pleasure.
And thank you for tuning in today.
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