The Evolution of HIPEC in the Treatment of Cancer

Transcript

00:00 --> 00:02Funding for Yale Cancer Answers is
00:02 --> 00:04provided by Smilow Cancer Hospital.
00:06 --> 00:08Welcome to Yale Cancer Answers
00:08 --> 00:10with Doctor Anees Chagpar.
00:10 --> 00:12Yale Cancer Answers features the
00:12 --> 00:14latest information on cancer care
00:14 --> 00:15by welcoming oncologists and
00:15 --> 00:17specialists who are on the forefront
00:17 --> 00:19of the battle to fight cancer.
00:19 --> 00:21This week it's a conversation about the
00:21 --> 00:23evolution of HIPEC and the treatment
00:23 --> 00:25of cancer with Doctor Kiran Turaga.
00:25 --> 00:27Doctor Turaga is a professor and
00:27 --> 00:29division chief of surgical oncology
00:29 --> 00:31at the Yale School of Medicine
00:31 --> 00:34where Doctor Chagpar is also a
00:34 --> 00:35professor of surgical oncology.
00:36 --> 00:38Dr. Turaga, maybe we can start off
00:38 --> 00:40by you telling us a little bit more
00:40 --> 00:41about yourself and what it is you do.
00:43 --> 00:45I'm a surgical oncologist,
00:45 --> 00:47which means I'm a cancer surgeon,
00:47 --> 00:49cancer first, surgeon second.
00:49 --> 00:51But I use surgical techniques
00:51 --> 00:54to remove cancers and my
00:54 --> 00:56focus has always been on cancers
00:56 --> 00:59that spread or are advanced.
00:59 --> 01:00Typically these cancers
01:00 --> 01:02are called Stage 4 cancers.
01:02 --> 01:04And my desire has been to
01:04 --> 01:07see how best we can treat these
01:07 --> 01:09cancers and potentially lead to
01:09 --> 01:11cures even in stage 4 settings.
01:12 --> 01:13You know, it's interesting
01:13 --> 01:16that you start in that way
01:16 --> 01:18because
01:18 --> 01:20you said a couple of things that
01:20 --> 01:22really tweaked my interest.
01:22 --> 01:24First, you said cancer first, surgery 2nd.
01:24 --> 01:26And the second thing you said
01:26 --> 01:29which was of interest was the fact
01:29 --> 01:31that you're interested in advanced
01:31 --> 01:33cancers and metastatic cancers.
01:33 --> 01:35For most cancers that we deal
01:35 --> 01:38with most of the time surgery is
01:38 --> 01:40limited to the early setting.
01:40 --> 01:44So can you talk a little bit about
01:44 --> 01:46how you got interested in advanced
01:46 --> 01:48and metastatic cancers even though
01:48 --> 01:51you're a surgeon or did that interest
01:51 --> 01:54in surgery come after the interest
01:54 --> 01:56in advanced and metastatic cancers?
01:57 --> 01:58That's a great question.
01:58 --> 02:00And my evolution
02:00 --> 02:02and interest of both cancer and
02:02 --> 02:04surgery was sort of parallel.
02:04 --> 02:05You know, I've personally
02:05 --> 02:06been affected by cancer.
02:06 --> 02:08My grandfather died of lung cancer,
02:08 --> 02:09my dad died of liver cancer.
02:09 --> 02:14And so there's certainly
02:14 --> 02:16a significant personal commitment
02:16 --> 02:19to wanting to do better for cancer.
02:19 --> 02:21I like doing things with my hands.
02:21 --> 02:23In fact, for the longest time I wanted to be
02:23 --> 02:26a medical doctor like an oncologist.
02:26 --> 02:28And then when I started doing
02:28 --> 02:30my rotations in surgery,
02:30 --> 02:32I really enjoyed it and I felt the
02:32 --> 02:33impact that we could have as surgeons.
02:33 --> 02:37And so it was just a marrying of my
02:37 --> 02:39two interests that brought me together
02:39 --> 02:41to doing oncologic surgery.
02:41 --> 02:43And I think you make a very good
02:43 --> 02:45point that surgery is
02:45 --> 02:47generally applied to tumors that
02:47 --> 02:49are early stage or even sometimes
02:49 --> 02:50for prevention of cancers.
02:50 --> 02:54But I think I was very affected by
02:54 --> 02:56many patients that I encountered
02:56 --> 02:58during both my training and then
02:58 --> 03:00even as a young attending where I
03:00 --> 03:02felt that patients who had cancers
03:02 --> 03:05that had spread were often treated
03:05 --> 03:07more with purely palliative
03:07 --> 03:10intent where you're trying to help
03:10 --> 03:12them live a little bit longer
03:12 --> 03:13with good quality of life,
03:13 --> 03:15but perhaps not really thinking
03:15 --> 03:17about curative approaches.
03:17 --> 03:19And so I started thinking about the
03:19 --> 03:21problem and I was fortunate to have
03:21 --> 03:22interacted with numerous individuals
03:22 --> 03:25that have had similar interests.
03:25 --> 03:28And so we were able to think
03:28 --> 03:30together about who are the patients
03:30 --> 03:32that we can actually be aggressive
03:32 --> 03:35even surgically to help think about
03:35 --> 03:36more curative intent approaches.
03:36 --> 03:38So that's sort of how
03:38 --> 03:39my journey evolved.
03:41 --> 03:43And so that leads us into
03:43 --> 03:46the whole world of of HIPEC.
03:46 --> 03:49Can you tell us a little bit
03:49 --> 03:52about what exactly it is and for
03:52 --> 03:55which patients it is appropriate?
03:56 --> 03:59HIPEC is hyperthermic
03:59 --> 04:00intraparitoneal chemotherapy.
04:00 --> 04:01So I'll tell you a little bit of a story.
04:01 --> 04:05Way back even in the 18th century,
04:05 --> 04:07there were patients that were
04:07 --> 04:08developing malignant ascites.
04:08 --> 04:11So they had fluid fill up inside their
04:11 --> 04:13abdomen and were very distressed.
04:13 --> 04:15And there was a surgeon who actually
04:15 --> 04:16put wine or alcohol inside the
04:16 --> 04:18abdomen with an intention of seeing
04:18 --> 04:20if it would dry up the fluid.
04:20 --> 04:22And it did, but unfortunately caused
04:22 --> 04:24such a significant reaction that
04:24 --> 04:26patients didn't do well from that.
04:26 --> 04:28But over the years,
04:28 --> 04:31there was this appreciation that cancers,
04:31 --> 04:33especially many cancers that start
04:33 --> 04:35both in the gastrointestinal tract,
04:35 --> 04:37so like our digestive system
04:37 --> 04:40and the genital urinary,
04:40 --> 04:42essentially in ovarian cancers, can
04:42 --> 04:45actually spread to the lining of the abdomen.
04:45 --> 04:46And as surgeons,
04:46 --> 04:47it was sort of overwhelming
04:47 --> 04:49to see the number of tumors
04:49 --> 04:51that were inside the abdomen.
04:51 --> 04:53And so back in the 1980s,
04:53 --> 04:57a concept was developed at the NIH/NCI
04:57 --> 04:59where chemotherapy was introduced
04:59 --> 05:02directly inside the abdomen at high
05:02 --> 05:03concentrations and high temperatures
05:03 --> 05:05with the understanding that when
05:06 --> 05:07it was delivered like that,
05:07 --> 05:11you were delivering a very high topical
05:11 --> 05:13concentration of the chemotherapy.
05:13 --> 05:14But the systemic absorption,
05:14 --> 05:15meaning the absorption
05:15 --> 05:17inside the bloodstream was
05:17 --> 05:18fairly limited.
05:18 --> 05:20And so this was termed different
05:20 --> 05:22things over the years.
05:22 --> 05:24And then finally in the early 2000s,
05:24 --> 05:26the combination of heat,
05:26 --> 05:27the intraperitoneal delivery,
05:27 --> 05:29meaning putting it inside the abdomen
05:30 --> 05:31and the chemotherapy came together
05:31 --> 05:33and it started being called HIPEC.
05:33 --> 05:35It is really delivering
05:35 --> 05:37high concentration chemotherapy at
05:37 --> 05:39high temperatures inside the abdomen
05:39 --> 05:42to essentially affect cancer cells
05:42 --> 05:44that are there after surgery with
05:44 --> 05:47an intention of trying to cure it.
05:47 --> 05:48It is a technique that's
05:48 --> 05:50used for many cancers, like I said.
05:52 --> 05:54But the common cancers that are routinely
05:54 --> 05:56treated with cytoreductive surgery
05:56 --> 05:59are ovarian cancers,
05:59 --> 06:01colon cancers, appendix cancers,
06:01 --> 06:04mesothelioma, and gastric cancer.
06:04 --> 06:05So those are sort of the big
06:05 --> 06:07cancer groups that are
06:07 --> 06:08often treated with this technique.
06:10 --> 06:12One of the other
06:12 --> 06:14things that's interesting is that when
06:14 --> 06:16we think about metastatic cancer,
06:16 --> 06:19most often we think that the cancer has
06:19 --> 06:22spread to a different part of the body,
06:22 --> 06:23often through the bloodstream.
06:23 --> 06:26And so it's interesting that you
06:26 --> 06:28mentioned that HIPEC is really
06:28 --> 06:32designed to be delivered topically
06:32 --> 06:35into the abdomen so that it has
06:35 --> 06:38its effect on peritoneal surfaces,
06:38 --> 06:40which seems kind of counter to how we
06:40 --> 06:42often think about distant metastatic
06:42 --> 06:45spread in the sense that we want to
06:45 --> 06:47get it into the systemic absorption.
06:47 --> 06:50Can you kind of talk about the rationale
06:50 --> 06:53behind that and and how that plays in?
06:54 --> 06:56Yeah, you know, I think this is actually
06:56 --> 06:59a fascinating story of how
06:59 --> 07:01medicine has evolved over the century.
07:01 --> 07:04So as you know, William Halsted was
07:04 --> 07:06a very famous cancer surgeon or a
07:06 --> 07:09surgeon at the Johns Hopkins Hospital
07:09 --> 07:11and he was of the belief that cancer
07:11 --> 07:13went in a very linear progression
07:13 --> 07:15and that if there was cancer,
07:15 --> 07:17the more aggressive and radical your surgery,
07:17 --> 07:19the better the chance of curing it.
07:19 --> 07:21So in fact taking out the entire chest
07:21 --> 07:23wall for patients with breast cancer,
07:23 --> 07:25cutting off legs for patients with
07:25 --> 07:27skin cancers on the leg, et cetera.
07:27 --> 07:29And that was sort of the way a lot
07:29 --> 07:30of cancers were treated all the way
07:30 --> 07:32up to the 1960
07:32 --> 07:34when nitrogen mustard which came
07:34 --> 07:37from World War 2 and chemotherapy
07:37 --> 07:39started being developed at that time.
07:39 --> 07:41And then subsequently there was the
07:41 --> 07:43Fisher's hypothesis which is where
07:43 --> 07:44the concept was,
07:44 --> 07:47all cancer is metastatic at diagnosis
07:47 --> 07:48that there's always cancer cells
07:48 --> 07:50or cancer DNA floating around in
07:50 --> 07:52your blood streams,
07:52 --> 07:54even if it's a very early stage cancer.
07:54 --> 07:57And so therefore there needs to be this
07:57 --> 07:59appreciation of all cancers have to be
07:59 --> 08:01treated with a combination of chemotherapy,
08:01 --> 08:04maybe surgery, and that is sort of how
08:04 --> 08:07you're trying to affect this entire system.
08:07 --> 08:09I think in the 1990s,
08:09 --> 08:11a concept called oligometastasis
08:11 --> 08:14was proposed by one of my
08:14 --> 08:15close friends and colleagues,
08:15 --> 08:19Ralph Weichselbaum and Sam Hellman who
08:19 --> 08:22noted that maybe the reality wasn't
08:22 --> 08:25one of these two hypothesis,
08:25 --> 08:27but actually somewhere in the middle
08:27 --> 08:29where there were clearly groups of
08:29 --> 08:31patients who had cancers that had
08:31 --> 08:33spread but had spread in a very unique
08:33 --> 08:35way where the spread was limited,
08:35 --> 08:38it was limited to a few areas and
08:38 --> 08:41when treated locally, meaning with
08:41 --> 08:43surgery or radiation or ablation.
08:43 --> 08:45So when you're actually working on these,
08:45 --> 08:47you can actually potentially cure
08:47 --> 08:49these patients of the cancer and
08:49 --> 08:51and this observation led to the
08:51 --> 08:53coining of the word oligometastases.
08:53 --> 08:55And since then there have been
08:55 --> 08:57numerous investigations in this
08:57 --> 08:58space and it's very fascinating to
08:58 --> 09:00think about the peritoneum itself.
09:00 --> 09:02The peritoneum is a remarkable barrier,
09:02 --> 09:04but if you actually look at it,
09:04 --> 09:05the peritoneum is like Saran wrap.
09:05 --> 09:07I tell patients it's sort of like
09:07 --> 09:09wallpaper on the walls of your rooms.
09:09 --> 09:12So it's a very, very thin layer.
09:12 --> 09:13But remarkably,
09:13 --> 09:14all cancer that generally start
09:14 --> 09:17in the peritoneum or in the
09:17 --> 09:18peritoneal cavity are actually
09:18 --> 09:19limited to that peritoneum.
09:19 --> 09:21It rarely invades beyond the peritoneum
09:21 --> 09:24into the abdominal wall or musculature,
09:24 --> 09:25things like that.
09:26 --> 09:28It's interesting when you
09:28 --> 09:30actually measure the DNA of cancer
09:30 --> 09:32that's present in the blood.
09:32 --> 09:34And this is some of our own work
09:34 --> 09:35where we've found that the DNA
09:35 --> 09:37that's shed by these tumors,
09:37 --> 09:38you might have a ton of
09:38 --> 09:39cancer inside the peritoneum,
09:39 --> 09:40but you barely will have any
09:40 --> 09:41DNA or cancer DNA
09:41 --> 09:43in the blood as opposed to if
09:43 --> 09:45you have one spot in the liver,
09:45 --> 09:47one spot in the lungs, you know,
09:47 --> 09:48the amount of DNA that's shed in the blood,
09:48 --> 09:50especially for colon cancer is tremendous.
09:50 --> 09:53So it's a very interesting phenomenon
09:53 --> 09:55where this may almost be a sequestered
09:55 --> 09:58form of metastases that is happening,
09:58 --> 09:59you know, in a certain region.
09:59 --> 10:01So I think that is where
10:01 --> 10:04the appeal of surgery and delivering
10:04 --> 10:05intraperitoneal chemotherapy
10:05 --> 10:07is significant in this area.
10:07 --> 10:10Yeah, it certainly makes
10:10 --> 10:12a whole lot more sense as to why
10:12 --> 10:15delivering chemotherapy in a more
10:15 --> 10:18topical way for people who have
10:18 --> 10:20peritoneal metastases may be beneficial.
10:20 --> 10:24Can you talk a little bit about how
10:24 --> 10:26efficacious it is in terms of the
10:26 --> 10:29response that patients have to HIPEC?
10:30 --> 10:32Yeah, I think that's a good
10:32 --> 10:33question and it's a complicated
10:33 --> 10:35answer because there are numerous
10:35 --> 10:38different cancers that are treated
10:38 --> 10:39with intraperitoneal chemotherapy.
10:39 --> 10:41But for instance,
10:41 --> 10:43one of the cancers or one of the
10:43 --> 10:45diseases that is often treated with this is
10:45 --> 10:47a condition called pseudomyxoma peritonei.
10:47 --> 10:49And this is a condition where patients'
10:49 --> 10:52abdomens are full of mucus that is
10:52 --> 10:54arising either from the appendix or
10:54 --> 10:56the ovary and it causes the entire
10:56 --> 10:58abdomen to fill up with mucus.
10:58 --> 11:01Folks often look like they're
11:01 --> 11:0339 weeks pregnant and it's just a very,
11:03 --> 11:05very tremendous burden on our patients.
11:05 --> 11:07In that population of patients,
11:07 --> 11:10especially the low grade tumors,
11:10 --> 11:1270% of the patients are cured of this
11:12 --> 11:13disease with cytopoductive surgery
11:13 --> 11:15and intraperitoneal chemotherapy.
11:15 --> 11:17So it is a very remarkable
11:17 --> 11:20effect on these tumors.
11:20 --> 11:21On the other hand,
11:21 --> 11:22when cancers are more high grade,
11:22 --> 11:24so they're more aggressive,
11:24 --> 11:26the cure rates are a lot lower.
11:26 --> 11:28So it's much harder to reach,
11:28 --> 11:29you know, 10 year survivals.
11:29 --> 11:31But I think for colon cancer, for instance,
11:31 --> 11:33if it's detected very early,
11:33 --> 11:35almost 60% of the patients
11:35 --> 11:36will live 5 to 10 years,
11:36 --> 11:39which I think is a good marker
11:39 --> 11:40for considering cure as opposed
11:40 --> 11:42to when it's detected late,
11:42 --> 11:43you know only 20% of the
11:43 --> 11:44patients will live five years.
11:44 --> 11:46So I think a lot depends on
11:46 --> 11:47when it's detected and then
11:47 --> 11:49of course how it is treated.
11:49 --> 11:51Also, the other thing that is often
11:52 --> 11:54misunderstood or mischaracterized
11:54 --> 11:57is HIPEC is not treatment by
11:57 --> 11:59itself without considering the
11:59 --> 12:01agent itself that's delivered.
12:01 --> 12:03It's merely a technology by which
12:03 --> 12:05you know therapy is delivered.
12:05 --> 12:07So the effects are
12:07 --> 12:09dependent on what the intraparitonal
12:09 --> 12:11chemotherapy agent is.
12:11 --> 12:14The problem with truly understanding
12:14 --> 12:17how efficacious or even effective
12:17 --> 12:18HIPEC itself
12:18 --> 12:21is a little complicated because
12:21 --> 12:22the first thing to consider is
12:22 --> 12:24is that it is often delivered with
12:24 --> 12:26surgery called cytoreductive surgery.
12:26 --> 12:27So I give patients the example,
12:27 --> 12:29like if you have grease that's
12:29 --> 12:31spilt in your room, you know,
12:31 --> 12:33instead of just spraying Lysol
12:33 --> 12:34on it or Febreze on it,
12:34 --> 12:36you first have to clean it all out.
12:36 --> 12:38You have to pick up all that grease,
12:38 --> 12:40scrub it and then you spray
12:40 --> 12:41the Lysol and then scrub it.
12:41 --> 12:44So that's really sort of the way HIPEC
12:44 --> 12:48works and it's in its core and you
12:48 --> 12:50know there are many components to it.
12:50 --> 12:51There's heat,
12:51 --> 12:52there's flow,
12:52 --> 12:54there's the drug that's delivered,
12:54 --> 12:56there's the duration that this is given.
12:56 --> 12:58And so it's very hard to
12:58 --> 12:59experimentally differentiate
12:59 --> 13:01which one of these components
13:01 --> 13:02is efficacious in which part.
13:02 --> 13:06But in randomized trials such as in
13:06 --> 13:08ovarian cancer and gastric cancer,
13:08 --> 13:11it has clearly been found to be
13:11 --> 13:12efficacious when certain agents are given.
13:13 --> 13:15But in colon cancer, when oxaliplatin,
13:15 --> 13:16one of the agents that's given,
13:16 --> 13:17it wasn't effective,
13:17 --> 13:18but mitomycin,
13:18 --> 13:20another agent was very effective.
13:20 --> 13:21So I think it's very individualized
13:21 --> 13:23based on the disease.
13:24 --> 13:26Fantastic. So we're going to pick up
13:26 --> 13:29this conversation right after we take
13:29 --> 13:31a short break for a medical minute.
13:31 --> 13:33Please stay tuned to learn more about
13:33 --> 13:35HIPEC and the treatment of cancer
13:35 --> 13:37with my guest doctor Kiran Turaga.
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14:57 --> 14:59You're listening to Connecticut Public Radio.
15:00 --> 15:02Welcome back to Yale Cancer Answers.
15:02 --> 15:04This is Doctor Anees Chagpar,
15:04 --> 15:06and I'm joined tonight by my guest,
15:06 --> 15:07Doctor Kiran Turaga.
15:07 --> 15:09We're talking about the evolution of
15:09 --> 15:12HIPEC in the treatment of cancer.
15:12 --> 15:14And right before the break, Kiran,
15:14 --> 15:17you were talking about the fact that
15:17 --> 15:20delivering this particular drug
15:20 --> 15:25depending on the disease in question,
15:25 --> 15:27delivering chemotherapy at a high
15:27 --> 15:30temperature into the peritoneal space,
15:30 --> 15:33it can potentially be curative
15:33 --> 15:35when coupled with surgery for
15:35 --> 15:37patients with metastatic disease,
15:37 --> 15:39which is something that a lot of
15:39 --> 15:41people may not really think about.
15:41 --> 15:44When we think about metastatic disease,
15:44 --> 15:47the words curative and metastatic
15:47 --> 15:49usually don't go together.
15:49 --> 15:52So a couple of questions just to wrap up
15:52 --> 15:54what we were talking about before
15:54 --> 15:57you had mentioned that the peritoneal
15:57 --> 16:00cavity is kind of like saran wrap.
16:00 --> 16:04And so one can imagine that the
16:04 --> 16:08chemotherapy may help to reduce
16:08 --> 16:11that amount of disease in people
16:11 --> 16:14who have significant burden of
16:14 --> 16:17metastases in their abdominal cavity.
16:17 --> 16:18The question then becomes,
16:18 --> 16:20can you really remove all
16:20 --> 16:22of that with surgery?
16:22 --> 16:23And if not,
16:23 --> 16:26how do you decide what to remove and how
16:26 --> 16:29do you decide if that's good enough?
16:30 --> 16:32Yeah, they're very, very good questions.
16:32 --> 16:35And I think the answer is
16:35 --> 16:37a process in evolution.
16:37 --> 16:39So the lining which is
16:39 --> 16:41on the abdominal wall side,
16:41 --> 16:43so essentially in the same
16:43 --> 16:45example of the room for instance,
16:45 --> 16:47being your abdominal cavity with
16:47 --> 16:49furniture inside it,
16:49 --> 16:50it's very easy to remove the wallpaper,
16:50 --> 16:52the flooring, the roof lining,
16:52 --> 16:55which is the the anterior peritoneum
16:55 --> 16:56or the parietal peritoneum.
16:56 --> 16:58So I think that's a fairly
16:58 --> 17:00straightforward procedure and
17:00 --> 17:02when I say straightforward you know
17:02 --> 17:04developed and you require expertise
17:04 --> 17:06but with training I think it's
17:06 --> 17:08possible for experts to do.
17:08 --> 17:09I think the part where it becomes
17:09 --> 17:11a little bit more challenging is
17:11 --> 17:13when the peritoneum overlying the
17:13 --> 17:16organs called the visceral peritoneum
17:16 --> 17:17especially over the intestines
17:17 --> 17:19is involved with the disease.
17:19 --> 17:23And so I think the key thing
17:23 --> 17:26that we know is that
17:26 --> 17:29removing tumors part way, halfway,
17:29 --> 17:31a little bit, doesn't help.
17:31 --> 17:33So I think the key part is in
17:33 --> 17:35selecting the patients in whom
17:35 --> 17:37we can remove all the disease or
17:37 --> 17:40reduce it to a microscopic level
17:40 --> 17:42such that the chemotherapy can work.
17:42 --> 17:44So I think the selection of patients
17:44 --> 17:46is very important and I think the big
17:46 --> 17:48factors that actually prevent many of
17:48 --> 17:50us from doing these surgeries would
17:50 --> 17:53be if there is extensive involvement
17:53 --> 17:54of the visceral peritoneum which
17:54 --> 17:56is the lining on the intestines
17:56 --> 17:58or the surfaces of the intestines
17:58 --> 18:00that cannot be feasibly removed.
18:00 --> 18:02I think the other thing also
18:02 --> 18:03as cancer surgeons, we all
18:03 --> 18:05think about very carefully with our
18:05 --> 18:07patients and shared decision making is
18:07 --> 18:09making sure that we are hitting the goals,
18:10 --> 18:12it's not just adequate
18:12 --> 18:13to live long or get cured,
18:13 --> 18:15if you're going to be living
18:15 --> 18:15a miserable life.
18:15 --> 18:18So I think it is very important to
18:18 --> 18:19balance both quality and quantity of
18:19 --> 18:21life when these decisions are being made.
18:22 --> 18:24Which of course brings us to
18:24 --> 18:26the next question, which is
18:26 --> 18:28can you talk about some of the
18:28 --> 18:31side effects of this procedure?
18:31 --> 18:33Yeah. So I think these side effects are
18:33 --> 18:35again broken down into the two components.
18:35 --> 18:37So one is the cytoreductive surgery
18:37 --> 18:39and these surgeries can be very,
18:39 --> 18:42very big where we're doing long operations,
18:42 --> 18:448 to 10 hours trying to clean out tumors
18:44 --> 18:47from every nook and cranny inside the
18:47 --> 18:49abdominal cavity requiring resecting organs,
18:49 --> 18:50sometimes many organs.
18:50 --> 18:53And so it could be very dramatic
18:53 --> 18:54or it could be very minor.
18:54 --> 18:55We're actually now doing
18:55 --> 18:56these laparoscopically.
18:56 --> 18:59In fact we just published along with
18:59 --> 19:01a bunch of other institutions a group
19:01 --> 19:02of laparoscopic procedures where you
19:02 --> 19:05can do these with little poke holes
19:05 --> 19:07and remove a lot of the cancers and
19:07 --> 19:08still achieve the same benefits.
19:08 --> 19:10The premise being you can identify
19:10 --> 19:11these cancers early,
19:11 --> 19:13which I think is the key to
19:13 --> 19:15thinking about the future of this.
19:15 --> 19:16And so the side effect profile of
19:16 --> 19:18the surgery is something that is
19:18 --> 19:20well known and well understood.
19:20 --> 19:22The addition of the HIPEC in
19:22 --> 19:25many randomized trials adds very
19:25 --> 19:27little to the complication profile
19:27 --> 19:29when studied in trial.
19:29 --> 19:29So essentially,
19:29 --> 19:31it can increase the risk of bleeding,
19:31 --> 19:32it can increase the risk of
19:32 --> 19:34leakages when we make connections.
19:34 --> 19:36But I think one of the things that we
19:36 --> 19:38notice often in clinics is that it does
19:38 --> 19:39knock the wind out of our patients
19:39 --> 19:41a little bit more than just surgery.
19:41 --> 19:44And so you know patients will typically
19:44 --> 19:46feel about 80% of their pre surgery
19:46 --> 19:48quality of life at about six weeks
19:48 --> 19:49and it takes about 3 months for
19:49 --> 19:51people to really start feeling as
19:51 --> 19:53well as they did before the surgery.
19:53 --> 19:54However,
19:54 --> 19:55interestingly in many quality
19:55 --> 19:57of life studies at six months,
19:57 --> 19:59most patients actually feel better,
19:59 --> 20:01like 120% as compared to prior
20:01 --> 20:02to surgery obviously because the
20:02 --> 20:04cancer has been removed and
20:04 --> 20:06they're doing well at that point.
20:07 --> 20:09Getting back to the question or
20:09 --> 20:12the point that you made earlier
20:12 --> 20:14which was that removing
20:14 --> 20:17a little bit doesn't really help.
20:17 --> 20:20I think a lot of listeners may have the
20:20 --> 20:22question that goes something like this.
20:22 --> 20:25If you have this peritoneum,
20:25 --> 20:27which is a barrier, right?
20:27 --> 20:30You had mentioned before the break
20:30 --> 20:32that people who have peritoneal
20:32 --> 20:35metastases often times don't have a
20:35 --> 20:38large burden of circulating cancer
20:38 --> 20:42that it really acts to confine that.
20:42 --> 20:46So then I wonder if you remove
20:46 --> 20:47the peritoneum,
20:47 --> 20:49do you then remove that barrier
20:49 --> 20:51such that patients who get a
20:51 --> 20:54recurrence may be more likely to
20:54 --> 20:55get distant metastatic disease?
20:56 --> 20:57That's a fascinating question.
20:57 --> 20:59And the answer is we
20:59 --> 21:00don't know completely,
21:00 --> 21:03but I can give you some data that might
21:03 --> 21:05help us think about this.
21:05 --> 21:07So if you think and again remember
21:07 --> 21:08unfortunately there's a very
21:08 --> 21:10heterogeneous group of tumors.
21:10 --> 21:11So it matters which cancer
21:11 --> 21:12we're talking about.
21:12 --> 21:14But let's take the example
21:14 --> 21:15of colon cancer for instance.
21:15 --> 21:17And so in colon cancer,
21:17 --> 21:19when the lining is removed,
21:19 --> 21:22the peritoneum is removed.
21:22 --> 21:25Depending on when the cancer comes back,
21:25 --> 21:27often the cancer will still come
21:27 --> 21:29back inside the abdominal cavity.
21:29 --> 21:30So even though the barrier or
21:30 --> 21:32the lining has been removed,
21:32 --> 21:34it still tends to come back to the cavity.
21:34 --> 21:37Now the caveat is that in colon cancer
21:37 --> 21:39we rarely remove the entire lining,
21:39 --> 21:40the parietal peritoneum.
21:40 --> 21:42And so perhaps there still is
21:42 --> 21:44that evidence of a barrier
21:44 --> 21:46that's keeping things at bay.
21:46 --> 21:47On the other hand,
21:47 --> 21:49there are tumors like mesothelioma
21:49 --> 21:50appendix tumors where we actually
21:50 --> 21:52take out the entire lining.
21:52 --> 21:53And even in those scenarios very
21:53 --> 21:55often if it does come back,
21:55 --> 21:57it still tends to come back
21:57 --> 21:58inside the abdominal cavity.
21:58 --> 21:59However,
21:59 --> 22:01one of the observations we started
22:01 --> 22:03noticing as a group most of us
22:03 --> 22:04that treat patients with this
22:04 --> 22:06disease was that we were now
22:06 --> 22:08keeping patients alive longer and
22:08 --> 22:10longer to the point where now
22:10 --> 22:12we started seeing metastasis or
22:12 --> 22:14spread of cancer in locations that
22:14 --> 22:15we wouldn't conventionally see.
22:15 --> 22:17So for instance in appendix cancer
22:17 --> 22:19we started seeing bone metastasis
22:19 --> 22:21or brain metastasis five years
22:21 --> 22:22after an operation.
22:22 --> 22:24So just a very unusual pattern.
22:24 --> 22:26So perhaps there may be some
22:26 --> 22:28effect of removing the peritoneum,
22:28 --> 22:31but not something that is immediately
22:31 --> 22:33observable or has been seen by datum.
22:34 --> 22:37And you know presumably this will take
22:37 --> 22:40longer study because distant metastases
22:40 --> 22:43won't occur in the short term.
22:43 --> 22:46And so it's interesting to kind of think
22:46 --> 22:49about getting these distant metastases
22:49 --> 22:52that we may not have seen before.
22:52 --> 22:54Which brings us to the
22:54 --> 22:56next big question I think,
22:56 --> 22:58which is can you talk a little
22:58 --> 22:59bit about ongoing research and
22:59 --> 23:02things that are most exciting for
23:02 --> 23:04you moving forward in this area?
23:04 --> 23:06Yeah. So I think
23:06 --> 23:08this is perhaps where we have
23:08 --> 23:10the opportunity for greatest impact,
23:10 --> 23:12which is number one,
23:12 --> 23:14I think knowing what this disease is.
23:14 --> 23:16So I think finally now there's
23:16 --> 23:18enough awareness and there's a lot
23:18 --> 23:20of folks that are learning more
23:20 --> 23:22about peritoneal metastases early.
23:22 --> 23:24And what is fascinating is a study
23:24 --> 23:26that was recently published where
23:26 --> 23:28patients with colon cancer without
23:28 --> 23:30metastases were treated with
23:30 --> 23:31intrapertonal chemotherapy with HIPEC
23:31 --> 23:34at the time of their operation.
23:34 --> 23:35So remember,
23:35 --> 23:37no peritoneal metastases and they
23:37 --> 23:40actually demonstrated that at three years,
23:40 --> 23:4297% of these patients who got the
23:42 --> 23:44chemo didn't have peritoneal metastases
23:44 --> 23:47versus 84 or 85% of patients in the
23:47 --> 23:49other arm who developed metastases.
23:49 --> 23:51So it's a remarkable
23:52 --> 23:54concept of thinking about can we act
23:54 --> 23:56in a preventative way or can we act
23:56 --> 23:59in a way where we find these diseases early.
23:59 --> 24:02I think the other thing is using
24:02 --> 24:03novel technologies like CFDN,
24:03 --> 24:05A/C, TDNA, advanced MRI,
24:05 --> 24:07advanced PET scans to find these
24:07 --> 24:09peritoneal metastases early so
24:09 --> 24:11that they can be treated earlier.
24:11 --> 24:13And then I think more importantly
24:13 --> 24:15finding better agents that can be put
24:15 --> 24:17inside the abdomen in better ways.
24:17 --> 24:19So there's technologies like HIPEC,
24:19 --> 24:22which is aerosolized chemotherapy,
24:22 --> 24:24but there's also other things such as
24:24 --> 24:26delivering immunotherapy inside the abdomen,
24:26 --> 24:29viruses inside the abdomen,
24:29 --> 24:31vaccines that I think have really moved
24:31 --> 24:33the field forward and are are exciting.
24:33 --> 24:36And what I tell a lot
24:36 --> 24:38of my patients is that while
24:38 --> 24:41we try our best to cure these cancers
24:41 --> 24:43and we're not successful all the time,
24:44 --> 24:45our goal is to at least keep people
24:46 --> 24:47alive long enough with good quality of
24:47 --> 24:49life such that our science advances at
24:49 --> 24:51a pace that we are able to see this.
24:51 --> 24:52And in my own lifetime,
24:52 --> 24:55as I'm sure you have seen Anees,
24:55 --> 24:57the advances in cancer care have
24:57 --> 24:58been dramatic.
24:58 --> 25:00You know for the first time we're
25:00 --> 25:02seeing reduction in cancer deaths nationally.
25:02 --> 25:04We're seeing almost two to
25:04 --> 25:07three new drugs being approved by the
25:07 --> 25:09FDA every month for many of these conditions.
25:09 --> 25:12And so I think it is remarkable to be
25:12 --> 25:15at this phase of science where
25:15 --> 25:17I feel much more hopeful about our, goals.
25:20 --> 25:24Yeah, you know the the idea of
25:24 --> 25:27of using HIPEC for preventing
25:27 --> 25:30peritoneal metastases is certainly
25:30 --> 25:33intriguing especially when you couple
25:33 --> 25:37it with this idea of you know the
25:37 --> 25:40the peritoneum being a barrier.
25:40 --> 25:44So has anybody looked at using just
25:44 --> 25:47the chemotherapy part of HIPEC in
25:47 --> 25:50terms of the prevention or in the
25:50 --> 25:51preventative trial that you mentioned,
25:51 --> 25:54were they also removing the
25:54 --> 25:55entire parietal peritoneum?
25:56 --> 25:59No. So I think 2 parts to the answer.
25:59 --> 26:02First for the trial
26:02 --> 26:04specifically called the HIPEC T4 trial,
26:04 --> 26:06it was removing the colon cancer
26:06 --> 26:08and then doing the hot chemo,
26:08 --> 26:10not removing the parietal peritoneum.
26:10 --> 26:12And so I think that was purely
26:12 --> 26:14a study where delivering the
26:14 --> 26:15intraparitonal chemotherapy with
26:15 --> 26:17mitomycin worked in colon cancer.
26:17 --> 26:19A similar study with oxaliplatin
26:19 --> 26:20actually didn't work.
26:20 --> 26:22So again going to the concept that
26:22 --> 26:24the actual drug that is delivered
26:24 --> 26:27matters a lot in these diseases.
26:28 --> 26:30I think the concept of putting
26:30 --> 26:32chemotherapy alone in the abdomen
26:32 --> 26:34is something that is being explored
26:34 --> 26:36both by a technology or technique
26:36 --> 26:39called intraperitoneal aerosol chemotherapy (PIPAC).
26:39 --> 26:41In both of these concepts,
26:41 --> 26:43if you think of the analogy I'd given
26:43 --> 26:45earlier of grease on the floor and
26:45 --> 26:46you know cytoreductive surgeries,
26:46 --> 26:48removing the grease and HIPEC is sort
26:48 --> 26:51of the Lysol or the Febreeze spray.
26:51 --> 26:53There is a concept where you actually
26:53 --> 26:55don't remove the tumor at all.
26:55 --> 26:56So you don't actually scrub
26:56 --> 26:58the grease and you just put the
26:58 --> 26:59chemotherapy inside the abdomen.
26:59 --> 27:00You let it
27:00 --> 27:01deliver either through HIPEC
27:01 --> 27:04which is heated and delivered inside
27:04 --> 27:06the abdomen or through normal
27:06 --> 27:07thermic intravertinal chemotherapy.
27:07 --> 27:09So you just put a catheter and you
27:09 --> 27:11put chemo inside it or with PIPEC
27:11 --> 27:13in which you actually aerosolize
27:13 --> 27:14the chemotherapy and put it inside.
27:14 --> 27:17And there are numerous trials that
27:17 --> 27:19are ongoing across the world where
27:19 --> 27:22these concepts are being studied not
27:22 --> 27:24just to improve quality of life,
27:24 --> 27:27but also to see if these are helpful
27:27 --> 27:29in controlling the cancers.
27:29 --> 27:31It is a little difficult to believe
27:31 --> 27:32that these therapies alone,
27:32 --> 27:33at least as they stand,
27:33 --> 27:35will lead to curative intent.
27:35 --> 27:37And so many of these are trials
27:37 --> 27:39designed with the end point of
27:39 --> 27:41being able to get to cytoreductive
27:41 --> 27:43surgery or some other modality.
27:43 --> 27:47But it has been very interesting to see many,
27:47 --> 27:49many preliminary reports where
27:49 --> 27:50intraparitonal chemotherapy delivered
27:50 --> 27:54in different forms seems to have
27:54 --> 27:55a significant oncological benefit.
27:57 --> 27:59And to your earlier point of you
27:59 --> 28:02know the whole concept of HIPEC
28:02 --> 28:03and cytoreductive surgery being
28:03 --> 28:06kind of studied as a bundle, right,
28:06 --> 28:09with the heat and the intraparitoneal
28:09 --> 28:11chemotherapy and the cytoreductive surgery.
28:11 --> 28:13One can only imagine that these trials
28:13 --> 28:16that are now ongoing which are looking at,
28:16 --> 28:19well what if we don't heat the chemotherapy,
28:19 --> 28:22what if we don't do the cytoreductive
28:22 --> 28:24surgery might give us some insight into,
28:24 --> 28:28you know, which of these elements of HIPEC
28:28 --> 28:30are really the most efficacious?
28:31 --> 28:31Absolutely.
28:32 --> 28:34Doctor Kiran Turaga is a professor and
28:34 --> 28:36division Chief of Surgical Oncology
28:36 --> 28:39at the Yale School of Medicine.
28:39 --> 28:41If you have questions,
28:41 --> 28:42the address is canceranswers@yale.edu,
28:42 --> 28:45and past editions of the program
28:45 --> 28:48are available in audio and written
28:48 --> 28:48form at yalecancercenter.org.
28:48 --> 28:51We hope you'll join us next week to
28:51 --> 28:53learn more about the fight against
28:53 --> 28:55cancer here on Connecticut Public Radio.
28:55 --> 28:57Funding for Yale Cancer Answers is
28:57 --> 29:00provided by Smilow Cancer Hospital.

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The Evolution of HIPEC in the Treatment of Cancer with guest Dr. Kiran Turaga December 24, 2023