Agent Orange and 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 with
00:08 --> 00:10your host Doctor Anees Chagpar.
00:10 --> 00:12Yale Cancer Answers features the
00:12 --> 00:14latest information on cancer care by
00:14 --> 00:16welcoming oncologists and specialists
00:16 --> 00:18who are on the forefront of the
00:18 --> 00:20battle to fight cancer. This week,
00:20 --> 00:22it's a conversation about the
00:22 --> 00:24role of Agent Orange in certain
00:24 --> 00:25cancers with Doctor Rory Shallis.
00:25 --> 00:27Dr Shallis is an assistant
00:27 --> 00:29professor of medicine in hematology
00:29 --> 00:31at the Yale School of Medicine,
00:31 --> 00:33where Doctor Chagpar is a
00:33 --> 00:34professor of surgical oncology.
00:35 --> 00:37So Rory maybe we can start off by
00:37 --> 00:39you telling us a little bit more
00:39 --> 00:41about yourself and what it is you do.
00:42 --> 00:43I'm originally from New Jersey,
00:43 --> 00:46South Jersey and in particular for
00:46 --> 00:48those that know there are difference.
00:48 --> 00:50Graduated from Rutgers College with
00:50 --> 00:52a BA and cell biology, neuroscience,
00:52 --> 00:55medical degree at the same place,
00:55 --> 00:58residency at Brown and then Fellowship and
00:58 --> 01:00Hematology Oncology at Yale was privileged
01:00 --> 01:02to stay on as faculty and currently
01:02 --> 01:04in the role of assistant professor.
01:04 --> 01:06I currently specialize in the
01:06 --> 01:08management of acute myeloid leukemia
01:08 --> 01:10and myelodysplastic syndromes.
01:10 --> 01:12Otherwise known as AML.
01:12 --> 01:14And MD S.
01:14 --> 01:16So that's generally my my practice.
01:17 --> 01:18Tell us a little bit more
01:18 --> 01:19about your research,
01:19 --> 01:21sure, so I mean,
01:21 --> 01:23my research is mostly focused.
01:23 --> 01:26As I said on patients that are
01:26 --> 01:27unfortunately afflicted with
01:27 --> 01:30AML and MD S but not dissimilar
01:30 --> 01:32from other folks that consider
01:32 --> 01:34themselves specialists in this area.
01:34 --> 01:36I do see, you know, a fair bit about
01:36 --> 01:38a fair bit of patience with them,
01:38 --> 01:39other myeloid malignancies and
01:39 --> 01:42other forms of leukemia as well.
01:42 --> 01:43Most of my research is and is by
01:43 --> 01:45way of clinical clinical trials,
01:45 --> 01:48but I do maintain an interest
01:48 --> 01:50in outcomes research as well,
01:50 --> 01:52and perhaps you know on some of the
01:52 --> 01:53topics that you wish to speak of.
01:54 --> 01:56Yeah, so so why don't we dive
01:56 --> 01:58a little bit more into myeloid
01:58 --> 02:01leukemias and and you can tell us a
02:01 --> 02:03little bit more about what they are,
02:03 --> 02:06what causes them, how common they are,
02:06 --> 02:08and what the prognosis is.
02:10 --> 02:12Them all you know pretty
02:12 --> 02:13important questions and all.
02:13 --> 02:15Could be pretty lengthy answers,
02:15 --> 02:18but I'll try to summarize it as best I can,
02:18 --> 02:18especially just considering you
02:18 --> 02:20know what I presume is going to be.
02:20 --> 02:22The audience here.
02:22 --> 02:25Myeloid leukemia is a general term actually,
02:25 --> 02:28and and taken simply refers to a
02:28 --> 02:30malignant state of the white blood cells.
02:30 --> 02:31More specifically,
02:31 --> 02:32those that are not lymphoid,
02:32 --> 02:342 general types and this is not
02:34 --> 02:36perfectly stated of white blood cells,
02:36 --> 02:37myeloid and lymphoid.
02:37 --> 02:40The myeloid group of cells originate
02:40 --> 02:42in the bone marrow or the essentially
02:42 --> 02:44what I tell patients is the factory for.
02:44 --> 02:46Where these are made and
02:46 --> 02:48once assembled or mature,
02:48 --> 02:49leave the marrow to enter the
02:49 --> 02:51bloodstream and perform their duties,
02:51 --> 02:52including fighting off infections
02:52 --> 02:54among a few other roles.
02:54 --> 02:56This is a near continuous process.
02:56 --> 02:57Unfortunately,
02:57 --> 02:59this process can be disrupted
02:59 --> 03:01by a number of mechanisms that
03:01 --> 03:03basically injure the machinery that
03:03 --> 03:05make healthy myeloid white blood
03:05 --> 03:07cells that can cause a ruckus on
03:07 --> 03:09the factory floor so that they're
03:09 --> 03:11really not made into the same
03:11 --> 03:12quantity but also the same quality.
03:12 --> 03:14We think with enough.
03:14 --> 03:17Injury to specific parts of that machinery.
03:17 --> 03:19The process can be stalled entirely in
03:19 --> 03:22certain areas where you know they are.
03:22 --> 03:24There's a backlog of the of the
03:24 --> 03:25myeloid white cell building
03:25 --> 03:27blocks or precursors that we call
03:27 --> 03:29blasts when in excess.
03:29 --> 03:31This generally heralds a typically
03:31 --> 03:33aggressive form of disease and at
03:33 --> 03:34a certain point defines what we
03:34 --> 03:36call an acute myeloid leukemia.
03:36 --> 03:38AML not every form of myeloid leukemia
03:38 --> 03:41or or even amount for that matter,
03:41 --> 03:42or are identical,
03:42 --> 03:44so you know this might be related to
03:44 --> 03:45the fact that there are different.
03:45 --> 03:46Parts of the machinery,
03:46 --> 03:48whether they are specific genetic
03:48 --> 03:49mutations in these cells or disruptions
03:49 --> 03:51of larger portions of these cells,
03:51 --> 03:53DNA called the chromosomes,
03:53 --> 03:55are detected and drive the cells
03:55 --> 03:58towards this usually unequivocally
03:58 --> 04:00problem problematic. State.
04:00 --> 04:01How common are they?
04:01 --> 04:04It's I mean it's all relative,
04:04 --> 04:05you know,
04:05 --> 04:07in the hematologic malignancy world,
04:07 --> 04:09there are some that are more common
04:09 --> 04:09than others.
04:09 --> 04:11When it comes to MD S and AML.
04:11 --> 04:13Generally we we regard the
04:13 --> 04:15incidence as being in the.
04:15 --> 04:17In the order of maybe three to four
04:17 --> 04:19per 100,000 population or person years,
04:19 --> 04:22so I wouldn't call them rare,
04:22 --> 04:23but I wouldn't call them common,
04:23 --> 04:26and the prognosis for each of these
04:26 --> 04:28diseases there's a lot of variance,
04:28 --> 04:29and this depends on.
04:29 --> 04:31Really a lot of variables and some
04:31 --> 04:33of which were really refining.
04:33 --> 04:36You know progressively and perhaps some we
04:36 --> 04:38haven't even really figured out just yet.
04:38 --> 04:39It can range from,
04:39 --> 04:40you know,
04:40 --> 04:42from just a patient being
04:42 --> 04:43recommended for observation.
04:43 --> 04:45You know it's something that can
04:45 --> 04:46be regarded as a chronic illness.
04:46 --> 04:47Like you know,
04:47 --> 04:49blood pressure issues or cholesterol issues,
04:49 --> 04:52and often doesn't really cause any problems.
04:52 --> 04:53Conversely,
04:53 --> 04:54there are patients that you
04:54 --> 04:55know have disease,
04:55 --> 04:56which is clearly aggressive and
04:56 --> 04:58comes with a whole host of problems
04:58 --> 04:59for which we have to be a bit
04:59 --> 05:00more aggressive. And our
05:00 --> 05:01and our management approach.
05:02 --> 05:05And So what? What causes us?
05:05 --> 05:07I mean, when we think about
05:07 --> 05:08other kinds of cancers,
05:08 --> 05:11sometimes we know an etiologic factor.
05:11 --> 05:14So for example, I think everybody kind of
05:14 --> 05:17knows that smoking can cause lung cancer.
05:17 --> 05:20We know that exposure to
05:20 --> 05:21sunlight can cause Melanoma.
05:21 --> 05:24We don't know too much about AML,
05:24 --> 05:25so talk a little bit about what
05:25 --> 05:27we do know and what we don't know
05:27 --> 05:29about factors that cause this.
05:30 --> 05:33Great question and and happy to help there.
05:33 --> 05:36There is evidence that some AML is
05:36 --> 05:38what we call quote UN quote de Novo,
05:38 --> 05:40meaning it arises quote from nothing
05:40 --> 05:42and quote to take the Latin literally.
05:42 --> 05:44But really, every you know every day our
05:44 --> 05:47marrow stem cells and their their cousins
05:47 --> 05:49or related cells are replicating and
05:49 --> 05:51there are inherent errors in the DNA that
05:51 --> 05:53come about and are usually, you know,
05:53 --> 05:56repaired via our really innate mechanisms.
05:56 --> 05:58But sometimes these aren't repaired,
05:58 --> 05:58you know?
05:58 --> 06:00So this is where some of this machinery.
06:00 --> 06:02Can be damaged and put the cells
06:02 --> 06:04in the path to become leukemic.
06:04 --> 06:05So it's really through no
06:05 --> 06:07fault of you know of their own,
06:07 --> 06:09but this is still kind of a
06:09 --> 06:11you know a A theory.
06:11 --> 06:13Beyond this we do know that you know,
06:13 --> 06:15as you stated there are several
06:15 --> 06:16causes to these disruptions to
06:16 --> 06:18the biology that previously normal
06:18 --> 06:20cells you know can become leukemic.
06:20 --> 06:22Probably the most well defined.
06:22 --> 06:24I would say our exposures to things
06:24 --> 06:26that are really meant to damage the
06:26 --> 06:28cellular DNA and for and for good reason.
06:28 --> 06:30These are certain chemotherapies.
06:30 --> 06:32And radio therapies.
06:32 --> 06:33Therapeutic radiation that you know is
06:33 --> 06:36used to be solid tumors like breast cancer,
06:36 --> 06:37lung cancer,
06:37 --> 06:38relatively common cancers,
06:38 --> 06:40and for which these therapies
06:40 --> 06:41you know are game changers.
06:41 --> 06:42These are effective therapies
06:42 --> 06:44and can cure a lot of cancer,
06:44 --> 06:46but there's a small but appreciable
06:46 --> 06:49risk that the marrow cells are exposed
06:49 --> 06:51to these these therapies and and the
06:51 --> 06:53damage they they they they induce,
06:53 --> 06:55and these cells acquire these
06:55 --> 06:57abnormalities and this increases the
06:57 --> 07:00risk of developing a myeloid leukemia.
07:00 --> 07:01Non therapeutic exposures which I think
07:01 --> 07:03is more to what you're getting at,
07:03 --> 07:04are also described, however,
07:04 --> 07:07so one of the clearest examples
07:07 --> 07:09of this are unfortunately I don't
07:09 --> 07:09wanna say a good example.
07:09 --> 07:12I'll say a clear example is are
07:12 --> 07:14there studies that have shown or
07:14 --> 07:16or looked at sort of the long term
07:16 --> 07:17outcomes of individuals that were
07:17 --> 07:19exposed to the radiation from the
07:19 --> 07:20atomic bomb explosions from,
07:20 --> 07:21you know,
07:21 --> 07:23the 1940s and Nagasaki and Hiroshima.
07:23 --> 07:25This is particle radiation,
07:25 --> 07:27specifically beta beta particles,
07:27 --> 07:30but also gamma radiation with regards to.
07:30 --> 07:33Other forms there is electromagnetic
07:33 --> 07:34electromagnetic radiation in certain
07:34 --> 07:36settings that are implicated.
07:36 --> 07:37Non therapeutic chemical exposures
07:37 --> 07:39are also shown in some studies,
07:39 --> 07:41including benzene.
07:41 --> 07:44Dioxin is formaldehyde as well.
07:44 --> 07:46Obesity has been linked to a
07:46 --> 07:47slightly higher risk of AML.
07:47 --> 07:49Other non modifiable risk factors
07:49 --> 07:51as we call them contribute as well,
07:51 --> 07:53one being male as there is a slight
07:53 --> 07:55predominance. The other is age.
07:55 --> 07:57AML is a disease.
07:57 --> 07:58Sorry for saying is a disease
07:58 --> 07:59that the elderly,
07:59 --> 08:00the median age at diagnosis is.
08:00 --> 08:02Around 68 years,
08:02 --> 08:05but the risk is higher the older you are.
08:05 --> 08:06And this might be because people
08:06 --> 08:07that have been on Earth longer,
08:07 --> 08:09they've had longer time to to be
08:09 --> 08:11exposed to the things that you
08:11 --> 08:12know we just discussed.
08:13 --> 08:16So you know, unpacking a few of the things
08:16 --> 08:18that you mentioned, the first thing,
08:18 --> 08:20and I'm sure that listeners who may
08:20 --> 08:23be on chemotherapy for a variety of
08:23 --> 08:25reasons or may have undergone therapeutic
08:25 --> 08:28radiation for a variety of cancers,
08:28 --> 08:30often think that you know these
08:30 --> 08:32therapies are are really trying to
08:32 --> 08:35treat whatever their malignancy is,
08:35 --> 08:36whether it's breast cancer,
08:36 --> 08:38colon cancer, lung cancer,
08:38 --> 08:41others that are are more common,
08:41 --> 08:44and so when you said there's a
08:44 --> 08:45small but still appreciable.
08:45 --> 08:50Risk of developing AML with these therapies?
08:50 --> 08:52How small is small and should people
08:52 --> 08:55really be scared that they are now
08:55 --> 08:57trading one cancer for another?
08:58 --> 09:00It's a very, very poignant
09:00 --> 09:02and important question,
09:02 --> 09:04and it's it's certainly relevant one,
09:04 --> 09:05you know, the risk depends
09:05 --> 09:07on a number of things.
09:07 --> 09:09The agents use the dose of radiation,
09:09 --> 09:10and to where these you know.
09:10 --> 09:12These agents are really being applied.
09:12 --> 09:15They're not very specific for tumor tissue,
09:15 --> 09:16they're just hopefully preferentially.
09:16 --> 09:18You know, damaging those cells.
09:18 --> 09:20Which are, you know if they're malignant,
09:20 --> 09:22or probably you know more apt
09:22 --> 09:24to to undergo the pathways that
09:24 --> 09:26drive them to death in a good way.
09:26 --> 09:28You know for the patient.
09:28 --> 09:29But if I had to kind of give
09:29 --> 09:30you a specific number,
09:30 --> 09:32it's in the order of single digit percents,
09:32 --> 09:34probably in the order of probably
09:34 --> 09:36no less than no less than 1%,
09:36 --> 09:38but probably no higher than the than 9%,
09:38 --> 09:40depending on the setting.
09:40 --> 09:42So you know there's a difference.
09:42 --> 09:46Say 1% is not 0% and it's not 0.001%,
09:46 --> 09:48there's always a a risk benefit calculation
09:48 --> 09:51on the provider side and always a risk
09:51 --> 09:53benefit discussion that should be had,
09:53 --> 09:55you know, in conjunction with
09:55 --> 09:56the patient you know before us.
09:56 --> 09:58Hopefully this conversation is open.
09:58 --> 10:00As it should be and thorough,
10:00 --> 10:02because this is like I said,
10:02 --> 10:03it's you know I don't want
10:03 --> 10:04to call it a nominal risk,
10:04 --> 10:05it is appreciable.
10:05 --> 10:07But as you've kind of just echoed,
10:07 --> 10:09you know these are effective therapies that
10:09 --> 10:12are shown to unequivocally increase the.
10:12 --> 10:14You know, not only the risk of the rates.
10:14 --> 10:16Sorry of of prolonged survival,
10:16 --> 10:17but cure for many,
10:17 --> 10:19many patients and you know,
10:19 --> 10:20as it stands right now,
10:20 --> 10:22these are still gold standards.
10:22 --> 10:24You know of care may be in,
10:24 --> 10:25you know,
10:25 --> 10:26the decades to come,
10:26 --> 10:27and hopefully in the not too distant future
10:27 --> 10:29you know the need for these therapies.
10:29 --> 10:31Might be maybe pushed aside or
10:31 --> 10:33slowly phased out with more
10:33 --> 10:35specific and less toxic therapies,
10:36 --> 10:39so which brings us to one or two
10:39 --> 10:41further questions to kind of unpack
10:41 --> 10:44that even further, so one is,
10:44 --> 10:46you know, you had mentioned that
10:46 --> 10:48the prognosis of AML really varies,
10:48 --> 10:49and for some patients it's
10:49 --> 10:51just a a chronic illness.
10:51 --> 10:54It's it's kind of it just follows along.
10:54 --> 10:56Just like you know,
10:56 --> 10:57hypertension or something else.
10:57 --> 10:58And it really doesn't cause
10:58 --> 11:00a whole lot of problems.
11:00 --> 11:02And other patients,
11:02 --> 11:05it can really be problematic.
11:05 --> 11:07Do we know whether the prognosis
11:07 --> 11:09is linked to the etiologic factor?
11:09 --> 11:10So, for example,
11:10 --> 11:12some people may be more willing
11:12 --> 11:15to trade one cancer for another
11:15 --> 11:17potentially or or even the risk
11:17 --> 11:19of developing AML if we knew
11:19 --> 11:21that the AML that was caused by
11:21 --> 11:24people who had been exposed to
11:24 --> 11:26chemotherapy for therapeutic intent
11:26 --> 11:30was really more of the benign.
11:30 --> 11:32Indolent kind of AML rather
11:32 --> 11:33than the more aggressive.
11:33 --> 11:35Do we know whether there's
11:35 --> 11:37any linkage based on ideology?
11:39 --> 11:40I probably say that biology matters,
11:40 --> 11:42and when I'm, you know,
11:42 --> 11:43that's sort of a, you know,
11:43 --> 11:46a vague a vague statement.
11:46 --> 11:48But really, it's you know what damage has
11:48 --> 11:51been induced in these leukemia cells or
11:51 --> 11:53the cells that eventually promote you.
11:53 --> 11:55Know the development of leukemia.
11:55 --> 11:59There are some exposures that are more
11:59 --> 12:01classically associated with particular,
12:01 --> 12:04you know, damage damages to the damage to
12:04 --> 12:09the DNA of of these leukemia cells some.
12:09 --> 12:10Are unfortunately,
12:10 --> 12:12you know pretty well described as
12:12 --> 12:14being predictive of stubborn disease
12:14 --> 12:17when it comes to things like prior
12:17 --> 12:18chemotherapies in particular,
12:18 --> 12:21classes of chemotherapies as
12:21 --> 12:23well as radiotherapy.
12:23 --> 12:25There are these are therapies
12:25 --> 12:27which are probably more associated
12:27 --> 12:29with what we call adverse disease,
12:29 --> 12:30adverse risk biology,
12:30 --> 12:32some things that can induce a
12:32 --> 12:34lot of DNA damage or chromosome
12:34 --> 12:36like large segments of DNA which
12:36 --> 12:38other chromosomes can be.
12:38 --> 12:39You know it just in and of
12:39 --> 12:41themselves sort of removed,
12:41 --> 12:44duplicated and there are some
12:44 --> 12:45poor risk lesions,
12:45 --> 12:48specifically one in TP 53 which
12:48 --> 12:51unfortunately is among those that.
12:51 --> 12:54Are the kind of the the worst to have
12:54 --> 12:57in a leukemia cell among other cancers,
12:57 --> 12:58and you know this is 1 lesion,
12:58 --> 13:00which is unfortunately the most commonly
13:00 --> 13:02observed across all the tumor types,
13:02 --> 13:04so it's not necessarily that
13:04 --> 13:06the the treatment itself is
13:07 --> 13:09independently predictive of prognosis.
13:09 --> 13:10It's more, say,
13:10 --> 13:13the the middle man that induces the
13:13 --> 13:15damage and the damage itself is
13:15 --> 13:17really what predicts more stubborn,
13:17 --> 13:18you know, disease, biology,
13:18 --> 13:20biology that would predict a lack
13:20 --> 13:21of response to frontline.
13:21 --> 13:22Therapies and unfortunately,
13:22 --> 13:25among patients that are, you know,
13:25 --> 13:28fortunate to achieve some form of remission.
13:28 --> 13:28Unfortunately,
13:28 --> 13:30don't stay in remission for that long,
13:31 --> 13:34and so you know the the last question
13:34 --> 13:38I'll ask you before we take our break is.
13:38 --> 13:40In the patients with AML who
13:40 --> 13:43have a more aggressive form,
13:43 --> 13:45is it treated with chemotherapy
13:45 --> 13:47and radiation, and if so,
13:47 --> 13:49couldn't that induce even more
13:49 --> 13:51toxicity like it does this
13:51 --> 13:53then become a vicious cycle?
13:56 --> 13:57If you were to ask a leukemia
13:57 --> 13:58specialist 20 years ago,
13:58 --> 14:00this would have been a shorter answer.
14:00 --> 14:01You know we're learning about this is
14:01 --> 14:03about the biology of disease and how this
14:03 --> 14:06can be sort of sub route based on the
14:06 --> 14:07mechanisms and classical combination,
14:07 --> 14:08chemotherapy has been the gold
14:08 --> 14:10standard for for many patients since
14:10 --> 14:11the early 1970s and this is still
14:11 --> 14:13the case for many subsets of disease.
14:13 --> 14:15This is what we call quote intensive
14:15 --> 14:16therapy and quote meeting and
14:16 --> 14:18has the potential to strain major
14:18 --> 14:20organs including the GI, tract,
14:20 --> 14:21kidneys, liver, heart, lungs,
14:21 --> 14:23and it will undoubtedly injure
14:23 --> 14:24the bone marrow, both bad cells.
14:24 --> 14:25In good cells,
14:25 --> 14:28just we hope the bad cells are the ones which
14:28 --> 14:31are preferentially yeah exposed and die.
14:31 --> 14:32As you can imagine,
14:32 --> 14:34at every patient can accept these risks
14:34 --> 14:35that come with intensive therapy.
14:35 --> 14:38The older patient or the the person
14:38 --> 14:39that already has strained organ
14:39 --> 14:42function might not be best suited to
14:42 --> 14:43really receive intensive therapy.
14:43 --> 14:45We do have less intensive therapies
14:45 --> 14:46that are reasonably effective and
14:46 --> 14:48this is really served as the backbone
14:48 --> 14:50upon which some of these newer
14:50 --> 14:51agents as you were alluding to,
14:51 --> 14:52you know,
14:52 --> 14:53have been studied and have been shown
14:53 --> 14:54to be better and and quite tolerable.
14:55 --> 14:56With the older intensive therapy quote,
14:56 --> 14:58UN quote ineligible patient this
14:58 --> 14:59then fosters newer combinations and
14:59 --> 15:01even the study of these combination
15:01 --> 15:03therapies in younger patients,
15:03 --> 15:05perhaps even those that are eligible for
15:05 --> 15:07intensive therapy at the starting line.
15:07 --> 15:09Well, we'll dive a little bit more
15:09 --> 15:11into all of the exciting developments
15:11 --> 15:13there right after we take a short
15:13 --> 15:15break for a medical minute.
15:15 --> 15:18Please stay tuned to learn more about AML,
15:18 --> 15:20its treatment, and about Agent
15:20 --> 15:22Orange right after we take a break.
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16:27 --> 16:29Welcome back to Yale Cancer Answers.
16:29 --> 16:32This is doctor Anees Chagpar and I'm joined
16:32 --> 16:34tonight by my guest Doctor Rory Shallis.
16:34 --> 16:39We're talking about a ML and you know how
16:39 --> 16:43this cancer of white blood cells really is?
16:43 --> 16:46The result of derangement of DNA that
16:46 --> 16:48can occur due to a variety of causes,
16:48 --> 16:51and we talked a little bit about
16:51 --> 16:53the fact that one of those causes
16:53 --> 16:57is actually therapies from cancer.
16:57 --> 17:00Treatments like chemotherapy or radiation,
17:00 --> 17:02which inflict DNA damage.
17:02 --> 17:05Now all of us know that.
17:05 --> 17:08The majority of these treatments tend
17:08 --> 17:10to be more targeted towards cancers,
17:10 --> 17:12which are rapidly dividing.
17:12 --> 17:15But what about people who don't
17:15 --> 17:18have cancers and who are inflicted
17:18 --> 17:21with DNA damage causing agents like
17:21 --> 17:24chemical weapons or doctor Shallis?
17:24 --> 17:26You mentioned before the break
17:26 --> 17:29things like radiation from nuclear
17:29 --> 17:30accidents or worse yet,
17:30 --> 17:34atomic bombs like Hiroshima and Nagasaki.
17:34 --> 17:36Can you talk a little bit more?
17:36 --> 17:39About how those have an implication in
17:39 --> 17:42terms of developing myeloid leukemias.
17:44 --> 17:46You said it quite quite nicely there.
17:46 --> 17:48Unfortunately, many patients are, you know,
17:48 --> 17:50unbeknownst to them and folks around them,
17:50 --> 17:52exposed to things that.
17:52 --> 17:55It might just take time in the order
17:55 --> 17:57of years to decades to understand
17:57 --> 18:00that these can be detrimental to
18:00 --> 18:01the genetic machinery you know,
18:01 --> 18:03DNA damage, and even some of the things
18:03 --> 18:06that can influence the machinery
18:06 --> 18:08that aren't necessarily DNA damage.
18:08 --> 18:10This is often accidental.
18:10 --> 18:12There are, you know,
18:12 --> 18:13chemical spills, contamination,
18:13 --> 18:15events and things that are used
18:15 --> 18:18in in a weaponized sense as well.
18:18 --> 18:21There is also an implication that there are.
18:21 --> 18:23Ambient forms of these potential
18:23 --> 18:24carcinogens or leukemogenesis you
18:24 --> 18:27know as we call them as a relates to
18:27 --> 18:29the development of myeloid leukemias.
18:29 --> 18:31There are several examples radiation.
18:31 --> 18:31We mentioned,
18:31 --> 18:33things like dioxin wins and you know
18:33 --> 18:34you know you had mentioned earlier the
18:34 --> 18:36break that you wanted to discuss a
18:36 --> 18:37little bit about ancient orange as well.
18:37 --> 18:38This is, you know,
18:38 --> 18:40one of the most infamous,
18:40 --> 18:42if not the most infamous sort
18:42 --> 18:45of vehicle by which one of these
18:45 --> 18:46agents leukemia genic agents,
18:46 --> 18:48was delivered to.
18:48 --> 18:48Unfortunately,
18:48 --> 18:50I would say innumerable individuals,
18:50 --> 18:51since we don't really know the full.
18:51 --> 18:52The full number.
18:53 --> 18:54So talk a little bit more about
18:54 --> 18:56Agent Orange. What is it?
18:56 --> 18:58What do we know about it?
18:58 --> 19:00What do we know about its implications
19:00 --> 19:02in terms of developing AML
19:03 --> 19:05Agent Orange? You know pervasive term,
19:05 --> 19:06but you know, in my experience,
19:06 --> 19:07many folks don't understand
19:07 --> 19:09what it actually is. It's it's.
19:09 --> 19:11It's essentially it's a
19:11 --> 19:12combination of herbicides.
19:12 --> 19:132 herbicide herbicides specifically
19:13 --> 19:15in one to one mixture,
19:15 --> 19:17both of which were commercially available
19:17 --> 19:20as early as the 1940s, you know.
19:20 --> 19:22And because it was an effective.
19:22 --> 19:23Herbicide it was used by the US
19:23 --> 19:25military during the Vietnam conflict.
19:25 --> 19:28As early as I want to say 1961 or 1962
19:28 --> 19:31as a defoliant meaning it would rapidly
19:31 --> 19:34clear thick areas of vegetation to
19:34 --> 19:37allow our forces to be more effective.
19:37 --> 19:38It was delivered by both air but
19:38 --> 19:40as well as ground there were,
19:40 --> 19:41you know, manual.
19:41 --> 19:43You know applicants going on
19:43 --> 19:44and throwing the same time,
19:44 --> 19:46but the herbicide spray missions you
19:46 --> 19:48know the aircraft were part of what
19:48 --> 19:50was called Operation Ranch Hand and
19:50 --> 19:52an estimated it was at least 15.
19:52 --> 19:54They wanna say 15 to 20 million gallons
19:54 --> 19:56gallons were delivered over these areas over.
19:56 --> 19:58You know the years that you know
19:58 --> 19:59the forces were in that area.
19:59 --> 20:02Agent Orange however, was found.
20:02 --> 20:02You know.
20:02 --> 20:04Unfortunately it took some time to,
20:04 --> 20:04you know,
20:04 --> 20:06realize this was found to be regularly
20:06 --> 20:08contaminated by a chemical known as
20:08 --> 20:09I'm not going to say the whole name,
20:09 --> 20:11but it's abbreviated as TCDD.
20:11 --> 20:13This is a specific form of
20:13 --> 20:16a benzo dioxin a dioxin.
20:16 --> 20:17These are as a group.
20:17 --> 20:18These are substances that are made
20:18 --> 20:20up of two benzene rings that are
20:20 --> 20:22joined chemically and really could be.
20:22 --> 20:23Unique by additions to,
20:23 --> 20:24you know,
20:24 --> 20:26usually through chlorine substitutions.
20:26 --> 20:27Unfortunately,
20:27 --> 20:30TCDD is a known carcinogen and
20:30 --> 20:31teratogen as well.
20:31 --> 20:33One of the first means by which
20:33 --> 20:35it was realized that Agent Orange
20:35 --> 20:37was a delivery mechanism for a
20:37 --> 20:38known toxin of this magnitude
20:38 --> 20:40was the fact that these areas of
20:40 --> 20:42Vietnam over the next few years
20:42 --> 20:43you know they did see an increase
20:43 --> 20:45in the rate of of birth defects,
20:45 --> 20:46and unfortunately a lot
20:46 --> 20:48of stillbirths as well.
20:48 --> 20:48Further study,
20:48 --> 20:50and this is mostly like lab and and
20:50 --> 20:52mouse based studies in the United States.
20:52 --> 20:54And around the same time,
20:54 --> 20:55given these findings clinically in
20:55 --> 20:57those areas led to the appropriate
20:57 --> 20:59conclusion that this was a problem,
20:59 --> 21:00and the US eventually did end
21:00 --> 21:02these missions and the use of
21:02 --> 21:03Agent Orange altogether,
21:03 --> 21:07and in 1971 as it relates to cancers.
21:07 --> 21:08And, you know,
21:08 --> 21:09I hopefully do get to talk about,
21:09 --> 21:11you know its relation to, we think,
21:11 --> 21:12and the myeloid leukemia realm.
21:12 --> 21:13A number of studies you know
21:13 --> 21:15if you know that have found an
21:15 --> 21:16increased risk of breast cancer,
21:16 --> 21:18GI cancer, some lung cancers,
21:18 --> 21:19kidney cancer,
21:19 --> 21:20you know these were well done studies
21:20 --> 21:22that showed that were basically,
21:22 --> 21:23you know, among patients that are
21:23 --> 21:25sorry folks that were exposed to.
21:25 --> 21:27TCDD, and not necessarily Agent Orange.
21:27 --> 21:29There is an appreciable risk
21:29 --> 21:30regarding the hematologic
21:30 --> 21:31malignancies or or blood cancers,
21:31 --> 21:33which is my area of expertise.
21:33 --> 21:35TCDD is linked to an increased
21:35 --> 21:37risk of both Hodgkin
21:37 --> 21:39and non non Hodgkin lymphoma,
21:39 --> 21:41as well as another malignancy
21:41 --> 21:43known as multiple myeloma.
21:43 --> 21:46The one rub is that you know exposure to TCDD
21:46 --> 21:49is uncommon and the disease is of interest.
21:49 --> 21:50You know are also uncommon and so and
21:50 --> 21:52some people also don't live long enough
21:52 --> 21:53to get these diseases of interest.
21:53 --> 21:55So you're studying an uncommon.
21:55 --> 21:58Among uncommon, with perhaps not enough time,
21:58 --> 21:59and this is likely why some other
21:59 --> 22:01studies have shown quote no increased
22:01 --> 22:03risk to which you know many of us say,
22:03 --> 22:04you know, have a you know,
22:04 --> 22:05raise an eyebrow.
22:05 --> 22:07However, the weight of evidence you know
22:07 --> 22:08in some is really clearly established.
22:08 --> 22:11That CD is a known carcinogen.
22:11 --> 22:13Its most critical designation you
22:13 --> 22:16know among some of the very well
22:16 --> 22:18respected communities and organizations.
22:18 --> 22:20The most I'd say weighted is the
22:20 --> 22:22International Agency for Research
22:22 --> 22:23on Cancer or IR,
22:23 --> 22:25which is the agency of the
22:25 --> 22:26World Health Organization.
22:26 --> 22:27And another relevant organization,
22:27 --> 22:29at least you know for the folks
22:29 --> 22:31you know about which we're talking.
22:31 --> 22:32You know veterans,
22:32 --> 22:33the Veterans Administration VA
22:33 --> 22:35also recognizes that there's enough
22:35 --> 22:37evidence to conclude that you know
22:37 --> 22:39exposure to TCDD via Agent Orange,
22:39 --> 22:42you know, was was causative,
22:42 --> 22:43and sorry,
22:43 --> 22:45it was associated in some cases causally
22:45 --> 22:47associated with the development of.
22:47 --> 22:48Several cancers.
22:50 --> 22:51And so if you're a vet and
22:51 --> 22:53you're listening to this show,
22:53 --> 22:57and you know that you were exposed,
22:57 --> 23:00what kinds of things should you be doing?
23:00 --> 23:01So number one?
23:01 --> 23:04Are there particular tests that you
23:04 --> 23:07should be doing in terms of screening?
23:07 --> 23:11We we know about screening tests
23:11 --> 23:14for breast cancer and colon cancer,
23:14 --> 23:19but not so much for leukemias #2.
23:19 --> 23:21Are there symptoms that you
23:21 --> 23:24should be looking for and #3?
23:24 --> 23:26Is there anything you can do
23:26 --> 23:28now that the exposures already
23:28 --> 23:31happened to lower your risk?
23:32 --> 23:34Good questions and I would probably
23:34 --> 23:35start by saying that you know more
23:35 --> 23:37than the patient shares the burden.
23:37 --> 23:40This is up to the provider to really
23:40 --> 23:42be mindful of exposures you know,
23:42 --> 23:44including you know Agent Orange exposure,
23:44 --> 23:45which at this point is usually
23:45 --> 23:47well documented and in fact the VA
23:47 --> 23:48really concedes that anyone serving
23:48 --> 23:50during a certain period of time in
23:50 --> 23:52a certain area has been exposed
23:52 --> 23:54to Agent Orange with regards to,
23:54 --> 23:56you know, cancer in general.
23:56 --> 23:57You mentioned some of the you know,
23:57 --> 23:58the clear.
23:58 --> 24:00You know, screening procedures for
24:00 --> 24:02certain cancers at the moment.
24:02 --> 24:04There's really no evidence to suggest
24:04 --> 24:06that you know that these practices
24:06 --> 24:08should be changed or altered in a way
24:08 --> 24:10just based on an exposure in the past.
24:10 --> 24:12When it comes to a new diagnosis
24:12 --> 24:14of myeloid leukemia like AML or I
24:14 --> 24:16would even consider MD S, you know,
24:16 --> 24:17patients can come to attention
24:17 --> 24:18in a number of ways.
24:18 --> 24:20We do see patients who have,
24:20 --> 24:21you know, as you said,
24:21 --> 24:22quote UN quote, routine blood work,
24:22 --> 24:24and there are abnormalities that you know
24:24 --> 24:25that eventually prompted evaluation.
24:25 --> 24:27But this is not common.
24:27 --> 24:27Typically,
24:27 --> 24:30there is a symptom that prompts blood work.
24:30 --> 24:31Whether this is something
24:31 --> 24:33as nonspecific as fatigue.
24:33 --> 24:34But also shortness of breath,
24:34 --> 24:36which is usually a consequence of anemia,
24:36 --> 24:37uncommonly bleeding,
24:37 --> 24:39which is usually a consequence
24:39 --> 24:40of low platelet count.
24:40 --> 24:42There are patients who present with
24:42 --> 24:44other complications of the disease,
24:44 --> 24:45either by way of it's inflammatory
24:45 --> 24:48nature such as fever or with true
24:48 --> 24:49infection because of a lengthy and
24:49 --> 24:51and low white blood cell count
24:51 --> 24:53that predisposes a patient to such.
24:53 --> 24:54Unfortunately, some patients,
24:54 --> 24:57you know do come to us much sicker,
24:57 --> 24:59with the clearly more aggressive
24:59 --> 25:01forms of the disease.
25:01 --> 25:01You know others, like I said,
25:01 --> 25:03with an isolated asymptomatic.
25:03 --> 25:06Blood count immorality but the need
25:06 --> 25:08for treatment is usually always sorry.
25:08 --> 25:10Is is always the same for pretty
25:10 --> 25:11much every patient.
25:11 --> 25:16So at the moment exposure doesn't
25:16 --> 25:18really buy the book by anyone.
25:18 --> 25:20Any change to sort of screening procedures,
25:20 --> 25:22but I would as a provider just knowing
25:22 --> 25:23that there's a history out there,
25:23 --> 25:25either documented or through you know,
25:25 --> 25:28our routine history and and physical
25:28 --> 25:30just has me a bit more mindful in
25:30 --> 25:32looking out for things and maybe
25:32 --> 25:33in a biased sense.
25:33 --> 25:35I do sort of change my my monitoring.
25:35 --> 25:36Practices from a CBC monitoring
25:36 --> 25:38standpoint or you know looking
25:38 --> 25:40for different things on exam that
25:40 --> 25:41might lend weight to hey,
25:41 --> 25:42we should be looking.
25:42 --> 25:43You know at this thing next or
25:43 --> 25:44do additional testing.
25:45 --> 25:47Is there anything that people
25:47 --> 25:48can do to prevent cancers?
25:48 --> 25:50Many, many patients kind
25:50 --> 25:53of ask about that, right?
25:53 --> 25:55Like, is there something that I should eat?
25:55 --> 25:58Should I try antioxidants?
25:58 --> 26:01What about hyperbaric oxygen?
26:01 --> 26:03What is your advice to to people
26:03 --> 26:05who have been exposed to Agent
26:05 --> 26:07Orange who are listening to this
26:07 --> 26:10show and are worried about the
26:10 --> 26:11fact that this increases their
26:11 --> 26:14risk and want to do something
26:14 --> 26:15proactively to reduce that risk?
26:17 --> 26:20Important, it starts with establishing care.
26:20 --> 26:22You know if we're talking about veterans,
26:22 --> 26:24and in particular many are not
26:24 --> 26:26really taking advantage of the
26:26 --> 26:28services to which they are entitled.
26:28 --> 26:30You know there is a a framework known as
26:30 --> 26:33service connection that is can be navigated
26:33 --> 26:35with some of the patient advocates and
26:35 --> 26:37the provider charged with the care.
26:37 --> 26:39For a veteran. You know,
26:39 --> 26:41especially one that was exposed to
26:41 --> 26:42Agent Orange that can secure you,
26:42 --> 26:44know additional benefits just
26:44 --> 26:45based on that exposure,
26:45 --> 26:46and anything that comes.
26:46 --> 26:47Down the road,
26:47 --> 26:49which at this point we can for the most part,
26:49 --> 26:52presume was related to that exposure.
26:52 --> 26:54So it starts with just establishing
26:54 --> 26:56care you know at the VA.
26:56 --> 26:58Or you know if you're not a
26:58 --> 26:59veteran and you know another,
26:59 --> 27:01another facility that can provide
27:01 --> 27:04really the same level of services,
27:04 --> 27:05what can be done otherwise beyond
27:05 --> 27:07the things we we talked about.
27:07 --> 27:08I don't want to sound like a nihilist
27:08 --> 27:09and forgive me for saying this.
27:09 --> 27:11But it's, you know,
27:11 --> 27:13and it's unlikely it is sorry.
27:13 --> 27:15It's likely that there will always
27:15 --> 27:17be cancer and and always be anal.
27:17 --> 27:17NBS,
27:17 --> 27:19mostly because of you kind of harkening
27:19 --> 27:21back to what you had just kind of mentioned.
27:21 --> 27:23You know the you know there
27:23 --> 27:25are things that are natural.
27:25 --> 27:26You know the natural world in which
27:26 --> 27:28we live is brutal and we're likely
27:28 --> 27:30being continually exposed albeit at
27:30 --> 27:32low levels to ambient things that are,
27:32 --> 27:34you know, likely naturally carcinogenic.
27:34 --> 27:36Unfortunately such as background
27:36 --> 27:38radiation from from radon for instance,
27:38 --> 27:39which is the leading cause of
27:39 --> 27:40the thought to be the you know,
27:40 --> 27:42the second leading cause of lung
27:42 --> 27:43cancer or cosmic radiation,
27:43 --> 27:45to which we will likely always
27:45 --> 27:46be exposed to some degree.
27:46 --> 27:47These are.
27:47 --> 27:48Extreme examples I'll give you,
27:48 --> 27:51but I think they serve the point.
27:51 --> 27:53This does not mean we should be lax
27:53 --> 27:55in coming up with alternatives, you know.
27:55 --> 27:56To spare exposure,
27:56 --> 27:57you know if we're talking about,
27:57 --> 27:59you know occupational exposures
27:59 --> 28:02as well as well as medical
28:02 --> 28:04exposures or the ambient setting.
28:04 --> 28:05It would be nice to have solvents
28:05 --> 28:07that are as efficient as a starting
28:07 --> 28:09material to make plastics, resins,
28:09 --> 28:11and spare workers to benzene,
28:11 --> 28:14to which we really don't know the true quote,
28:14 --> 28:15unquote safe level.
28:15 --> 28:17You know, which I think is a misnomer.
28:17 --> 28:18Or chronic low dose exposure that
28:18 --> 28:20you know a body like like OSHA,
28:20 --> 28:21for instance, establishes.
28:21 --> 28:23It's possible that there may be
28:23 --> 28:25no safe exposure to anything out
28:25 --> 28:28there which can be invoked as a
28:28 --> 28:29carcinogen or leukemogenesis to bring
28:29 --> 28:32it back to my my area of interest.
28:32 --> 28:34Doctor Rory Shallis is an assistant
28:34 --> 28:36professor of medicine in hematology
28:36 --> 28:39at the Yale School of Medicine.
28:39 --> 28:41If you have questions,
28:41 --> 28:43the address is canceranswers@yale.edu
28:43 --> 28:45and past editions of the program
28:45 --> 28:48are available in audio and written
28:48 --> 28:49form at yalecancercenter.org.
28:49 --> 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
28:55 --> 28:57Radio. Funding for Yale Cancer Answers
28:57 --> 29:00is provided by Smilow Cancer Hospital.

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July 10, 2022

Yale Cancer Center

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