"Liver Cancer Clinical Care and Research at Yale" and "Dermatologic Toxicities in Cancer Patients: Updates from the Yale Onco-dermatology Clinic"

May 25, 2021

Yale Cancer Center Grand Rounds | May 25, 2021

Mario Strazzabosco, MD, PhD and Jonathan Leventhal, MD

Information

ID: 6627
To Cite: DCA Citation Guide

Download Transcript

00:00To this week's character center Grand rounds,
00:03we have two speakers today,
00:04both from Yale will give us
00:07some exciting discussion of some
00:08of the work we're doing here.
00:10Our first speaker is Mario Strozza busco.
00:13He's a professor of medicine, director
00:15of the liver Cancer program here in Co.
00:18Director of the liver center.
00:20He received his medical and PhD degrees
00:22in Italy and then had a number of
00:25leadership positions at the University
00:26of Milan before joining our faculty.
00:28He's an expert on the care of
00:30patients with liver cancer,
00:32is internationally known for
00:33his work and hepatology.
00:34Liver transplantation is a member
00:36of several scientific societies
00:37in Europe in the United States.
00:39His current research relates to
00:41the pathophysiology of biliary
00:43tract disease is repaired.
00:45Biology of liver repair,
00:46liver transplantation,
00:47liver cancer in healthcare management,
00:49and so today we're going to hear from
00:52Mario and tell of his talk is liver cancer,
00:56clinical care and research at Yale.
00:58So Mario, you're
01:00up. Thank you very much, Dan,
01:02for the introduction and thanks for the
01:05Cancer Center for the Invitation Ann.
01:07And thanks a lot for this Milo.
01:12Cancel. After the program has
01:15received during this year,
01:17I'm really only as a as a spokesperson
01:20for for a group of colleagues that are
01:24interested in India in the in liver
01:27cancer and treating liver cancer.
01:29So I'm just the messenger.
01:31So what do we do in the liver
01:35cancer program we take?
01:36We take care of patients with liver
01:39masses either benign or malignant are,
01:42and the two most frequent.
01:44Primary liver cancer are able to sell cash.
01:49You know my also called HTC and
01:53Intraparticle Angela carcinoma and I
01:56focus my talk today mostly on ATC,
01:59which is the most important primary.
02:04Cancer of the liver.
02:05The liver is is an organ which
02:09is located in the abdomen,
02:11but really here it is.
02:13The main regulator of the whole body,
02:16metabolic coma stasis,
02:18and in fact if the liver fails we actually,
02:22the patient suffered of a
02:24syndrome which is very bad.
02:26Absolutely Poly systemic syndrome.
02:28As you can see here.
02:30And the important thing
02:32to understand is that 85%.
02:3490% of the patient with able to sell casino.
02:38They are also cirrhotic in
02:40the liver and not only that,
02:43but if we follow a cohort of patients
02:46with viral induced liver disease
02:48either B or C for enough time,
02:51we see that the main the.
02:55When they die,
02:56most of them they died with the in a
03:00particular casting armor as shown here.
03:03So why what the about the circus
03:06number is actually only rise
03:08worldwide and the estimate are there.
03:11There are 830,000 cases recorded every year,
03:15with the mortality that almost
03:17approached the incidents.
03:18And why is that? Well, this is the.
03:22A result of a number of worldwide the
03:26epidemics that are also risk factor
03:29for chronic liver disease and among
03:33them we can mention viral appetite is B&C.
03:37You see that they the infection
03:40from viral potatis is hundreds
03:43of millions of people I call is
03:47another important work by the.
03:49What is factor as it is obesity,
03:52diabetes?
03:53And more and more,
03:55we realize that if 50 important risk
03:58factor is due to inequality's an patient
04:02population that are underserved and
04:05they have difficulties in reaching
04:07and being reached by the best care,
04:11other risk factors,
04:12smoking alpha toxin and and an other as well.
04:17And this is important to understand that
04:20the combination of risk factor increases.
04:23And actually the risk.
04:24So in every patient that we see,
04:26we need to look for all of them.
04:33This risk factor are distributed
04:37unequally in the world wide.
04:41For example, aflatoxin is more frequent
04:43as it goes in in the African continent,
04:46but if we go to the US, All told,
04:49this publication shows Nash is a main factor.
04:52It is actually we have all the
04:54respect or combining here because
04:56we have Nash with alcohol,
04:58we have appetite is C.
05:00And so on. And in fact,
05:02if we look at the distribution of
05:06the incidents of ATC in the US.
05:09We see that is actually particularly
05:13hygge about 8. Per 100,000 in the.
05:19Massachusetts, Connecticut and New York.
05:22So if we look back more.
05:26In depth into it,
05:27we see that in the US the liver
05:30cancer incidence has increased almost
05:32three times in the last 30 years,
05:35and the mortality is increased
05:37almost two times as shown.
05:39Also in this graph on the right,
05:41if we look at the numbers and
05:44compare the number with two big.
05:47GI killers in their adjustive system,
05:50like bankers and call,
05:52and we see that in Connecticut
05:55we have a record of 480 cases per
05:58year and this is a combination
06:00between HCC an intra Patrick.
06:05Cinema also the interparticle
06:07answer carcinoma is really minority,
06:09so we have 480 new cases and $320
06:13unfortunately and this is a figure
06:16which is similar to another big
06:18killer like the pancreatic cancer.
06:21730 and 520. So what?
06:27How does the molecular
06:29pathogenesis of apples for casino?
06:31We have said it.
06:35Most of the patients have cirrhosis
06:38and in fact the main theory is
06:41that in the cirrhotic nodule
06:43there are Even so happens that
06:45brings to Korando casino man.
06:48I'm in one of these is the.
06:52Alter the.
06:55TRT promoter that basically.
07:01Blocks the ability of the liver
07:04cell under information to undergo
07:06senescence and an among them.
07:09There are other possible.
07:12But the genetic event like P53,
07:15which is basically associated with aflatoxin,
07:17better cotton imitation,
07:18and so on and so forth.
07:21But this is a scenario that
07:22is not very well understood.
07:25All we can say for now is as
07:27there are two different classes,
07:30one name proliferation,
07:31the other non proliferation that are
07:33different in terms of their prognosis
07:35and in terms of their ability to
07:38respond eventually to immunotherapy.
07:42So I put the cell carcinoma is
07:45a very peculiar cancer because
07:47he has a 2 dual personality.
07:50It's a cancer in a failing
07:52vital organ and it can be seen
07:55from a biological perspective.
07:57There are inflammation induced phenomenon,
07:59oncogenic viruses,
08:00literally natural general mutational
08:02landscape and this brings to a complex
08:05tumor fenotype with the witches aggressive.
08:07It is a terror generals with
08:10a high recurrence rate.
08:12When is Sonic Liquor point of view?
08:15We have any plastic disease
08:17and the liver disease,
08:18and so the street.
08:19The treatment strategy has to
08:21be tailored according both to
08:23the tumor stage and the function
08:26of stage liver disease,
08:27and this creates some of the peculiar
08:30things in that management of this disease.
08:33So we don't have one single way to
08:35manage it that you have resection
08:37ablation came embolization value
08:39or addition therapy.
08:41Systemic therapy still has a.
08:43At growing Bastille small role,
08:45we have the possibility to
08:47transport the patient.
08:48The only solid organ that can be
08:51transplanted and most of these
08:53patients actually die because
08:54of liver failure and in fact one
08:58professional figure that is involved in this.
09:00It is the hepatologist.
09:04What, because of all this,
09:07different professionals involved
09:09in in this in the treatment,
09:12the entry points usually are multiple
09:15Ann and this multiple entry points
09:18in the system creates different
09:21trajectory for the patient with way.
09:25Dispassion of resource is an an can
09:27impact on the outcome because there is a
09:30confusion and you don't really know what
09:33the part where the patient should follow.
09:35And this is one of the reason why it
09:38is important to have a team work.
09:41So to give an example,
09:43probably will take the whole day to this
09:46guy to figure out how to change the tires,
09:49whereas the Formula One team can
09:51do it exactly in 2.5 seconds.
09:54Which is amazing and is this love?
09:57Is this out of their coordination of care?
09:59So treatment of Apple Circus nominees,
10:01coordination of care,
10:02and this is the trajectory that the
10:05program has followed through the year.
10:07So we started as a conference and I
10:10remember this few people with me wrong.
10:12Salom Jeff Pollack.
10:14Jeff Wayne Rubber Dam part starting
10:16this little room and then he
10:18grew to a tumor board.
10:19Thanks to Tamar Daddy and then
10:21now it's becoming a program.
10:23And maybe it's really it's
10:25it's ready for the next step.
10:28So when it became a program
10:30we designed in IDL structure,
10:33which is the patient can come into
10:35the system through a single point.
10:38Still working on that aspect,
10:40and then it's actually discussing the
10:43tumor board where they treat him,
10:45allocation happens and is allocated
10:48to the different specialty according
10:50to the best treatment are an.
10:52After that it gets follow-up be 'cause
10:55we need to treat the risk factor.
10:58We need to mind the liver.
11:01Help us some chemo prevention protocols
11:04and mirroring this clinical operation.
11:06There is also research component
11:09which is again a team effort.
11:13So where are we? So we begin with the.
11:16This is a map of the Smiler Care center
11:20OK and this is the two main site for
11:23liver care here at again you have in
11:26hospital and the VA off without but
11:29through the recent year there was
11:31open a site in in Bridgeville with
11:34magnetic so insight in the ambari
11:37came to stand for my shift key.
11:39James Mattis T is,
11:41you know,
11:42the westerly side and soon Alan
11:44Jaffe will go to West for now.
11:47This is in combination with with
11:49the with the transplant team
11:51with which we have a very good
11:53long standing collaboration.
11:55Now it really takes a village to treat
11:58this cancer and here you can see.
12:01Not all of their colleagues that
12:04participates and I have to say it's
12:06it's a real privilege to be able
12:08to work with these individuals,
12:11and they are extremely skilled.
12:13All of them are leaders in their
12:15own right are in their own field,
12:18and so the discussion that we have
12:20are so enlightening and we follow a
12:23like a structure of discussion going
12:25through and analyze the reception,
12:27the transplant candidacy,
12:28the OR whether we need to use local
12:31regional treatment like ablation,
12:33criminalization, radiation.
12:34It's I don't have the time to go into this,
12:38but it's it's every single all of this
12:41possible treatment is very complex
12:43and the decision making is a is
12:45even more complex because it depends
12:48from systemic and local factors,
12:50and in fact we really an.
12:52We basically follow the Barcelona
12:54Liver cancer treatment, which is a.
12:58Used by master Lever Societies an
13:01but it really has a lot of troubles.
13:04OK, there are changes.
13:06This is the latest version and
13:08takes into account liver function,
13:11performance status and and then
13:13atomic location of the cancer.
13:15But really there are lot of
13:17troubles and we cannot be so
13:20strict with the categories and for
13:22example this was written in 2019.
13:25Now the first line treatment
13:27is that is above but.
13:29Cannot be only confined to
13:31patient at about to die,
13:33as in this staging system,
13:34so a lot of things have changed
13:36and that made difficult by the
13:38fact that we have multiple theology
13:41at the underlying liver disease.
13:43The frequent comma abilities in fact,
13:45this is a cancer.
13:47That picture above 65 years of age.
13:50Multiple treatment option and
13:5170% of them have a recurrence of
13:54the cancer in the next 20 months.
13:57We have liver transplantation
13:59and other actors,
14:00so the only way to maintain a.
14:04Structure approach this is to is
14:07to that room and board with four
14:09hours is not a way where we present
14:12strange cases is really the machine
14:14Ann and the credit for this goes to
14:17my colleague and friend to Mark Addy,
14:20who set it up and now we we
14:22discussed 13 cases each week.
14:25Last year we even with the kovit
14:27we discuss 520 cases and one of the
14:30busiest actually tumor Board 2 of
14:33200 of them with new cases we have.
14:35300 patient and follow up.
14:37150 new cases and these actually
14:40treated in several different ways,
14:42but this is not the venue to to go
14:46through the volumes or to their substantial.
14:50The tumor board is also where we
14:52got ideas for research and ideas
14:55for for improvement and innovation.
14:57This is that list of items that we
15:00discussed at the last steering committee.
15:03For example,
15:04several of this question that I'm
15:06not going to read all of them, but.
15:11Generate. Recent opportunities.
15:13Anne Anne, Anne,
15:16Anne and also great care I I wanna
15:18go briefly through this case.
15:20This was a patient. Refer to doctor.
15:23She's key for transfer evaluation
15:25Mike so the patient realized that
15:27he had actually liver cancer.
15:29And Moran had infiltrative
15:31hepatocellular carcinoma with with
15:33the tumour portal vein thrombosis.
15:35So we discussed the case at the
15:38tumor board and it was decided that
15:41there was no other option rather than
15:45medical treatment or offering a trial.
15:48Stacy did try to give him
15:50softening by the beginning I,
15:52but this was denied by the insurance
15:55and so it happened at Stacy
15:57adjust open atrial at the initial
16:00trial with a diesel Bev,
16:01which is now you know,
16:03the first line treatment for back
16:06in that time was actually we were
16:09very lucky that we could offer
16:12him and as you see here.
16:14In the graph of plotting
16:16the alpha fetoprotein,
16:18he had a complete response.
16:22But in the next two years,
16:24this patient was completely and the
16:26quality of life of this patient,
16:28which was completely altered
16:30by recurrent severe episodes of
16:32portosystemic several opathy.
16:33As you can see here from the ammonia
16:35and actually in during one of
16:38these emission it also discussion
16:39about goals of care was initiated,
16:42so we had a patient who was treated by
16:45with you from this malignant tumor.
16:47But he was dying because I believe
16:50this is an act.
16:51.2 very bright hepatologist wanagas
16:54intervals with system are in,
16:57another is stalled.
16:58Slacker, which is an interventional
17:01hepatology calling,
17:02decided to embolize his plane arena.
17:05Shanta and now the patient is
17:08functional cancer free, happy.
17:10And when he refers to what
17:13happened with the insurance,
17:15he quotes wisdom churches saying pessimist
17:17sees difficulty in every opportunity,
17:19an optimist sees opportunity
17:21in every difficulty.
17:22So this is a case which we learn
17:25a lot about it an an in fact.
17:28Now particularly,
17:29you know,
17:30one of the things that was interesting
17:33in the Gary case was that he
17:35never had a recurrence an will.
17:37I said occurrences,
17:39something that playing sour
17:40patient 6070% of them in there.
17:43In their first two years,
17:45so that prompted the opening of a
17:48try again by Stacy and D'istria
17:51will actually try to address
17:53the role of adjuvant treatment
17:56after surgery or ablation.
17:59Another tria is being brought
18:01here by David Madore.
18:03Fu actually addresses and
18:04other nuances of this,
18:06so he his aim is to understand
18:09whether there is a benefit in what
18:12we call combination treatment.
18:14So the idea to combine came
18:16embolization with the.
18:20Even on Koleji, in combination with a PKI.
18:23And another important aspect of the
18:26program is the fact that we really tried
18:29to record and measure the outcomes.
18:32Ariel's affair with John awfully.
18:38My tarantula Shapiro at there are curating
18:41a database of 1000 patients in India
18:44and the survival code divided by BCSC
18:47states that you see, here are our own.
18:51Outcomes so we can really.
18:55Make the termination letter based on.
18:57Now our environment in expertise
18:59and is simple example that the
19:01outcome is outstanding up to more
19:03than three years for this campaign
19:06patient with initial cancer,
19:07things are changing after this an and
19:10there's a lot to be discussed in among
19:13these patients and I I don't have it here,
19:16but if anybody has a doubt
19:18about transplantation,
19:19I can tell you that the code was transfer
19:22stations like this so outstanding long term.
19:25Result for the few patient again get it,
19:29but this is a very,
19:30very important aspect of what we do
19:33an an it's going to be so complex
19:36that in fact Julius with Jim Duncan
19:38Manderly and John actually very much
19:41involved in trying to understand
19:43the use that we can have artificial
19:46intelligence in the diagonal.
19:47This characterization treatment of this
19:50Council and we expect that this would
19:53be a great aid to our decision making
19:56and also discovery of new approaches.
19:59So what the liver cancer program
20:03doesn't have a formalized?
20:08Visas program but is actually
20:10the assembly of of several
20:13different interrested people.
20:15What have we done to.
20:19Put together these people so the
20:21first thing that we have been doing
20:24with Julius De Mar is is these liver
20:27cancer talks their monthly in the
20:30late late afternoon on Thursday.
20:32Each of them with two or three percent
20:35Asia and this has to be ongoing.
20:38Research are now published work.
20:40It covers all the aspects, clinical,
20:42translation and healthcare and and this
20:44actually this approach Spark collaboration.
20:46There were paper grant application
20:48and also a big step.
20:50Forward was at last October when again
20:53with the help of the Miami Justice Ann,
20:57and thanks to the help of Gary Honeycutt's
21:00and his team in the Cancer Center,
21:03we put forward the first liver cancer
21:06Super Summit which is called pre
21:09Lude because he was not in person.
21:11Where was Virtu are,
21:13but the mission was to address the
21:16Uncle logic challenges or liver cancer
21:19to the collaboration amount of abide.
21:22Spectrum will be a faculty.
21:24And I'm I'm gonna really run through
21:27some of this visa suspect and what
21:30in what I call the Commonwealth to
21:33liver cancer is at yeah OK because
21:36it's not again formalized structure,
21:38but is the gathering of of interested
21:41people coming from the medical school,
21:43the School of Public Health?
21:45the VA system involving departments
21:47like surgery, internal medicine,
21:49the Cancer Center, the year,
21:51liver cancer,
21:52the Department of Pathology and
21:54so on and so forth.
21:56But all these people actually.
21:58In a 2019-2020 publish it 72 papers,
22:02an 38 of them original article 7R
22:05position paper 14 reviews and 14 of them
22:09are actually publishing in journals
22:12with an impact factor around or above 20,
22:16which I think is pretty remarkable.
22:19So just a very quickly glancing through it.
22:23The number of our faculties
22:26are actually involved.
22:28In studying the different risk
22:31factors that I mentioned before,
22:33so we have outstanding work
22:35performing virally theology,
22:37interaction with aging,
22:38the HIV.
22:39We have food program that addresses
22:42the obesity,
22:43diabetes and affolder alcoholic liver
22:46diseases in other regions branch
22:49which is which is growing an Ann
22:51and also health care disparities.
22:54An for example.
22:57Razor,
22:57osean and other faculties are addressing.
23:03Some of the. Differences that
23:05we see even in connecticu.
23:07So for example, as you can see here.
23:11The incidence of HCC is clearly
23:13higher in this panic and black
23:16population and hopefully will will
23:18try to nail down what the causes are.
23:21So outstanding results in outcome research,
23:26mostly addressing the role of
23:30surveillance and and all of.
23:37Antiviral treatment and the
23:38growing group of faculties are
23:40also interested in concert cost,
23:42effectiveness and care delivery.
23:44We do a lot of things,
23:46but we don't really know their value
23:49in terms of cost effectiveness,
23:51so this is another growing area.
23:54Translation studies that also growing and
23:57just to mention several faculties in Basic,
24:01more basic studies are interested
24:03in the transition between Nashville,
24:06roses and and cancer and in human
24:10Hansa ran and a lot of people
24:14is actually interesting in the.
24:18Role of the tumor micro environment.
24:22Which this is, I think,
24:24is very interesting.
24:25This is staining for Alpha,
24:27SMA, identifying fiber,
24:28ask cancer,
24:29associated fibroblasts in
24:31cholangiocarcinoma and in hepatoma
24:32you see two very different.
24:38Pathology Ann and these are correlated
24:40to two very different aggressiveness.
24:43Also the tumor let me very briefly
24:45mention some of our work in the macro
24:48environment or the calendar carcinoma
24:51showing the central role of calf or
24:53the Cancer Society fiberglassed in
24:55determining several of the aspects
24:58of the two Moran now our Co other
25:01colleagues are addressing this
25:03using single cell transcriptomics.
25:05This is also an interest of
25:07our colleagues in radiology.
25:09They're trying to use.
25:12The tools of radiology to generate reliable
25:15imaging biomarkers for immunotherapy.
25:17This is I, I think,
25:20it's granted or or or proposed for
25:23the NIH by David matter of MGM Duncan
25:28interest on the metabolic aspect is also.
25:32Followed by by Michael Nathanson,
25:34lab, and here is work from Emma
25:37tells where I'm like nothing.
25:39So I'm looking at the IP3 receptor and
25:43mitochondrial functionality in 80C and CCA,
25:46and they're all in in the in chronic
25:49affect like like existence of up doses
25:52or generating up talking factor of
25:55this was published very well last
25:58year and and finally mentioning.
26:01Tell you who,
26:03just join and the chair of pathology is,
26:06you know, a very well renowned liver cancer
26:10researcher and is doing several things.
26:13Among this he explaining to
26:15detect circulating metallated
26:16DNA as an early diagnosis.
26:19Wait, you see,
26:20and we're really looking forward very
26:23much to this study is an an also.
26:26He is trying to is using
26:29Kartiana Glypican 3 as a target.
26:32Hopefully not that big of a TC
26:34and and I'm I'm gonna finish
26:37now because the time is over.
26:39But you know this is just an example of the
26:43richness of the research that that we have.
26:46And really this is and I have to
26:49thank all the department that are
26:52involved in this enterprise and.
26:55You know each of these department.
26:58There are some hepatologist hiding
27:00there and and this is what what
27:03will I call your liver,
27:05which is a very old tradition.
27:08Here is going to celebrate
27:11the Diamond Jubilee.
27:12Next year and I thank you for your attention.
27:17Thank you very much, Mario.
27:19Very interesting talk. Are there
27:20any questions from the audience?
27:29I can start with one.
27:30So recently drugs have been developed
27:33that will cure hepatitis C virus.
27:36What fraction of people in
27:38this country are affected?
27:39People are being treated by these drugs.
27:41And what's the effect on liver cancer?
27:44Tell the the the strategy would be
27:47worldwide application of of HPV and
27:50therefore I would say that a growing
27:52amount of patients she is being
27:55treated should be treated that has had
27:58like a slowing down during the COVID
28:01crisis but should resume full time.
28:04The question of the effect on liver
28:06cancer is a very good question
28:09because there has been a great
28:12controversy becauses a lot of patient.
28:14After eradication of the virus,
28:16have the path surprised that
28:18delivered Carson happens.
28:19Anyway, this is happening in patients
28:21that were treated already with
28:24significant fibers in their liver.
28:26And it was initially proposed
28:27that actually the allocation of
28:29the virus would get rid of some
28:31kind of beneficial information,
28:33but further studies have shown that
28:35actually the the risk is decreased,
28:37but it's not zero.
28:39So why is not zero is something
28:41that we need to understand.
28:43My personal opinion is that we are simply
28:46eliminating one of the many risk factors.
28:48You know the the regular guy is
28:51a guy that didn't know to have
28:53actitis is a little overweight,
28:55has smoked.
28:56Is drinking, you know,
28:58not drunk but enjoying the wine Ann.
29:03It just doesn't know it an an therefore yeah,
29:06will you ever you have four risk
29:08factor of which you eliminate one?
29:10This is why this is a internal medicine.
29:13This is right because you really
29:15have to address all the risk
29:17factor in every single patient.
29:19Otherwise,
29:19you may fail like like the
29:22eradication of appetite is C shows
29:24in certain patients and so the
29:26basic clinical recommendation is
29:27that the patient that you were ever
29:30advocated while he was erotica still
29:33needs to undergo the six months.
29:36Screening and surveillance for ACC.
29:41Are there other other questions?
29:49OK, with that I I do see the vineyard
29:52behind your folder there in moderation.
29:56Yeah moderation, OK thank you.
29:57Thank you very much.
29:59Mario, thank you, thank you.
30:01So our next speaker today
30:04is is Jonathan Levinthal.
30:06Who is, I'm sorry, just lossed.
30:10My CHEAT SHEET here.
30:13So Jonathan is assistant professor
30:15of Dermatology and the director of
30:17the Yale Uncle Dermatology Clinic.
30:19He received his MD degree from New York
30:22University and is residency here at Yale.
30:25He specializes in caring for
30:27patients with skin cancer,
30:28beginning with skin screening programs
30:30to detect cancers and sun damage and
30:33optimize prevention and therapy.
30:35The clinic serves a dermatologic
30:37needs of cancer patients dealing
30:39with a variety of skin issues,
30:41including skin changes due to
30:43chemo therapies, can infections.
30:44Cancer involvement in the scan,
30:46radiation, dermatitis,
30:47and other changes due to radiation,
30:49so we'll hear that today.
30:50So Jonathan I'm looking forward
30:52hearing you talk. Thank you.
30:54Thank you so much and it's a
30:56real pleasure to be here today.
30:58So today I'm going to talk about
30:59dermatologic conditions in cancer patients,
31:01and I'm going to provide updates
31:02from the ankle dermatology program.
31:05So here is a list of my disclosures,
31:08mostly from serving on advisory
31:10councils with fellow Aqua dermatologist
31:12throughout the country looking at
31:14skin toxicities as well as some
31:16clinical trial research funding.
31:17So the objectives of the talks I
31:19wanted to start by introducing you
31:21to the Aqua dermatology program.
31:22Then I wanted to discuss the importance
31:24of cutaneous toxicities and how they
31:26can impact patients quality of life
31:27as well as their cancer therapies.
31:29When severe, I wanted to highlight
31:30some of the most common toxicities
31:32that I see from select targeted
31:33and immune checkpoint inhibitors
31:34and also traditional chemotherapy
31:36as well and discuss the role that
31:38aren't with their mythology.
31:39Plays at a Cancer Center.
31:41So for some background,
31:43the Uncle Dermatology program was
31:44established by my great mentor and friend,
31:46Jennifer Choi.
31:47Shortly after she graduated residency
31:49and then I had a great opportunity
31:51when she got recruited to Northwestern
31:53as a chief resident to start seeing
31:55patients in the clinic for which
31:57I've led the clinic ever since.
31:59And we've really seen a tremendous
32:00outgrow of support from so many
32:02colleagues in Metanx terjung Radon,
32:04an anthology,
32:05and the clinic has really grown
32:06dramatically over the years.
32:08It's a very robust, busy clinic.
32:10Some days we see up to 50 patients.
32:12And I just have a great team of
32:15nurses residents as well as research
32:17fellows and and support from the Yale
32:19Center for Clinical Investigation.
32:21So the field of supportive Uncle
32:23Dermatology really blossomed in
32:24the 1990s with the advent of many
32:26different targeted kinase inhibitors,
32:28which skin toxicities were so common
32:30in almost the majority of patients
32:32and it really encompasses many
32:33different things that we service,
32:35so there's definitely all the toxicities
32:37that we see from the systemic therapies,
32:39radiation therapies,
32:40graft versus host disease as well
32:42as complications from cancer.
32:43Going to the skin with metastases,
32:45but there's really a lot of other
32:48indirect complications that we treat
32:49in clinic and that includes paranoia.
32:51Plastic disease, infectious complications,
32:53especially in patients who are
32:55immuno suppressed as well as being
32:56part of the survivorship program.
32:58For many patients who have
32:59survived cancer now,
33:00an increased risk for developing
33:02cutaneous carcinogenesis and then
33:04also part of the umbrella is that
33:06the Melanoma program I'm part of.
33:07It falls under the umbrella of
33:09Uncle Dermatology and so a lot of
33:11what I do is also high risk in
33:13cancer screening to diagnose and
33:15treat many different types of skin
33:18cancers and also collaborate with
33:20the cancer genetics program to
33:22obtain tissue for genetics.
33:23So wanted to start by discussing the
33:26cutaneous toxicities are not just cosmetic.
33:28These are really important issues
33:29that impact patients quality
33:31of life and there's been many
33:32studies over the years looking at
33:34validated quality of life surveys.
33:36Anan.
33:36It's just so so common for these
33:39toxicities to to impact in both
33:41physical as well as emotional domains
33:43and so one interesting concept is that
33:45women seem to be affected greater
33:47than men in terms of their quality
33:49of life and it's probably because
33:51of the types of regiments they
33:53did receive for breast and.
33:55Other gynecological cancers which
33:56frequently impact the here in the nails,
33:58and so this can affect women's self image,
34:01cultural identity,
34:02sexuality as well as mental health.
34:04Feelings of depression, anxiety,
34:06and a loss of control over their body.
34:09The hallmark examples
34:10chemotherapy induced alopecia,
34:11which we see from the cytotoxic agents,
34:13in particular an one homework study,
34:15showed that almost 60% of women with
34:17breast cancer preparing for chemo
34:18considered this to be the worst
34:20possible associated side effect
34:21and almost 10% even considered
34:23declining treatment in fear of it.
34:25So these are real,
34:26very real and important issues,
34:27and there's been so many other studies
34:29looking at the acne acne reform,
34:31ranch hand, foot rashes,
34:32nail changes in mucus, itis,
34:34all of which I'm going to discuss
34:36in which can impact quality of life.
34:39So the study on the left kind of
34:41highlights an important concept that
34:43it's not just those main toxicities that
34:46can impact patients quality of life.
34:48In this study of targeted agents
34:50in breast and colorectal cancers,
34:52you'll see that things like itching,
34:54dryness of the skin, easy bruise ability,
34:56pigmentary changes,
34:57they can all be associated with
34:59with poor quality of life and the
35:02study on the right looked at the
35:04different types of chemotherapy and
35:06how they impact quality of life.
35:08And not surprisingly.
35:09A lot of the more novel,
35:11targeted therapies,
35:12especially the EGFR inhibitors,
35:13were associated with an increased
35:15number of skin toxicities,
35:16but also those which impact quality
35:19of life greater than some of the
35:22traditional chemotherapeutic agents.
35:23Unfortunately,
35:24there's mounting data showing that
35:26early dermatologic intervention
35:27can really make a difference,
35:29and so Uncle dermatology programs
35:31have been showing up at most of
35:34the premier cancer centers in
35:36the States and abroad,
35:37and one study from MSK show that with
35:40outpatient Uncle dermatologic involvement,
35:42patients on immunotherapy were less
35:44likely to have interrupted treatment
35:465% versus 30% to those managed
35:48without dermatologic intervention.
35:50In a recent study by the
35:52Harvard Group similarly showed.
35:54The inpatient konsult can also
35:55decrease the chance of patients
35:56receiving systemic immune suppression
35:58and immune therapy discontinuation.
36:00Now,
36:00we haven't performed a comparative study.
36:02We did perform a very large
36:04study recently that was published
36:06of over 100 immunotherapy.
36:07Rash is 1/4 of which presented to my clinic,
36:11often with disruption of immunotherapy.
36:12But with early dermatologic intervention,
36:14over 90% of these patients were
36:16able to remain on their treatment,
36:18so I think these numbers are compelling.
36:21So wanted to start by focusing
36:23on some of the toxicities that
36:25I see from targeted therapy.
36:27I mean there's so many different
36:28types of agents to discuss,
36:30I think I'm just going to
36:32review some of the main ones.
36:34In the interest of time so the EGFR
36:36inhibitors are a class that are commonly
36:38associated with cutaneous toxicities.
36:39Not surprisingly,
36:40as the epidermal growth factor
36:42receptor is expressed in the skin,
36:43hair and nails, and really important
36:45for homeostasis and some of the
36:47monoclonal antibodies likes to talk
36:49some mad panitumumab as well as
36:51the 1st and 2nd generation drugs.
36:53Presents with cutaneous toxicities
36:54in the majority of cases.
36:55Fortunately, the third generation
36:57drugs like OC murdered him
36:58for a lung cancer patients.
37:00They don't seem to get the rest,
37:02the rest nearly as often,
37:03probably less than 30%,
37:04and so the most common toxicity
37:06that we see is the papulopustular
37:08for the acne or form rash,
37:10and this usually manifests on patients face,
37:12scalp, chest and back.
37:13Although it could be widespread
37:14and one common misconception is
37:16that it's just a sterile technique.
37:18Reform drug eruption, which is true.
37:19However,
37:20I find a large percentage of these patients.
37:22Especially when they get to higher grades
37:24often have coinfection with staff.
37:26Both M RSA an MSA,
37:28so that's a good therapeutic Pearl
37:30to obtain wound cultures and hear
37:32examples of the Packers and pustules.
37:34Note all this year is crusting.
37:36It was all in petition eyes with staff.
37:38Oreius is a more typical scenario
37:40in one of the more robust severe
37:42toxicities that might require
37:44more aggressive treatment,
37:45which I'll discuss.
37:46We see lots of nail infections
37:48paronychium and because of the
37:49piercing of the nail plate into
37:51the hyponychium patients can get
37:53this friable granulation tissue
37:54known as pyogenic granulomas.
37:56These can be exquisitely tender
37:57and painful and definitely impacts
37:59patients quality of lights.
38:00It's not uncommon to see her
38:02growth abnormalities,
38:03including elongated eyelashes.
38:04Some patients have a hard time
38:06trimming their eyelashes,
38:07which are curving inward
38:08and irritating their eyes,
38:10so they'll just see me analysis
38:12them with with cutting their
38:13eyelashes we see lots of dryness and
38:16painful cracks and fissures too.
38:18There is an example of,
38:19you know a patient who presented
38:21with a neck near former option which
38:23was in petition eyes with staff.
38:25She responded quite well to Doxie,
38:27cyclin topical steroid ointments,
38:28antibiotic ointments.
38:29And I'm a big fan of antiseptic
38:31soaks like aluminum acetate removed
38:33a serious crusting.
38:34Here's another example of a patient.
38:36Also recently from the Lung Cancer
38:37Group who also had quite a severe
38:39acne deformed mesh occasionally in
38:41very severe circumstances there can
38:43actually be associated alopecia as well.
38:45She responded very well to
38:47dermatologic intervention.
38:47I wanted to highlight that.
38:49While the acne reformers typically
38:50presents during the first few
38:52weeks on the head, chest and back,
38:54we have seen uncommon presentations as well,
38:56which are described in the literature
38:58and those are prepared drug eruptions
39:00which likely fall into the category
39:01of the late acne reform toxicity.
39:03In these cases usually present
39:05many months into treatment,
39:06and they often present on the
39:07lower extremities in the buttocks,
39:09and as you can see with these
39:11perperek looking lesions,
39:12and they're also frequently Co
39:14infected with staff on Moon culture.
39:17Here's an example of a patient with
39:19head and neck cancer who responded
39:21to dermatologic intervention.
39:23And here's an example of a patient
39:25who has pretty
39:25typical pyogenic granuloma with Paronychium,
39:28who responded to the topical
39:30beta blocker timolol gel.
39:31Many of these cases are non responsive
39:33to conservative approaches and sometimes
39:35procedural intervention may be required,
39:37like using silver nitrate to court arise
39:40these granulomas or even nail avulsion
39:43for the really recalcitrant cases will do.
39:46So there's many hot topics around EGFR
39:48inhibitors one over the years has been
39:50looking at pre emptive versus reactive
39:51therapy and there's various phase two
39:53trials which have shown that doc see
39:55cycling Minocycline with with topical
39:57steroids and moisturizers can actually
39:58reduce the severity of the rash.
40:00The overall incidence is probably not
40:02affected and I think the approach towards
40:04the rest differs depending on the program.
40:06Here they've been looking at lots of new
40:08novel approaches for treating the rash,
40:10none of which are really
40:11gained widespread use.
40:12Some of the data is very mixed with
40:15these drugs and so we definitely need.
40:17New approaches and then I just wanted
40:19to briefly mention that there's a few
40:21clinical trials which we're doing here.
40:23Studying the rash one is currently
40:24recruiting and I really appreciate
40:25my awesome collaborators in the head
40:27and neck and thoracic group which
40:29are helping to recruit patients.
40:30And that's to better understand the
40:32microbiome of the populations or option
40:34and see how changes in the microflora
40:36can be associated with the severity of
40:38the rash and response to rash treatment.
40:40And then there's a company that we're
40:42working with that's developing a
40:44novel probiotic with staff epidermal
40:46disappointment to look to see if
40:48this is going to reduce secondary
40:50infections with staff wareus,
40:51which are commonly associated
40:52with severe rashes.
40:53And so this is in development
40:56hoping to do this trial next year.
40:59So shifting gears,
41:00I wanted to briefly discuss
41:01other targeted agents,
41:02which we see a lot of toxicities
41:04from in the breast group.
41:06They heard two inhibitors as well
41:08as American hitters used for various
41:10cancers can actually share some of
41:12the properties of the EGFR inhibitor.
41:14Reactions will often see folliculitis,
41:16eruptions and acne or form rashes.
41:17However,
41:18they usually less severe and less frequent.
41:22I wanted to talk about another very
41:24important toxicity which comes to
41:26clinic and that's the hand foot
41:27skin reaction.
41:28So these usually develop from
41:29the anti angiogenesis agents,
41:31some of which we just heard about
41:33which are used in the paddle cellular
41:35carcinoma such as the anti veg F agents.
41:37And here's a list of the FDA approved
41:39ones and so this seems to be one
41:42of those toxicities which just so
41:44frequently impacts patients quality of life.
41:46They have a hard time being able
41:48to work to do their daily routine.
41:50It very often impacts their activities
41:52of daily living.
41:53Patients usually present early on.
41:55We just kind of thickening or hyper
41:57keratosis of the palms and soles,
41:59but then over time they get these
42:01very painful.
42:01Callous is,
42:02sometimes they are inflamed and
42:04then in the severe cases we even
42:06see blisters develop as well.
42:08This rash can be associated with very
42:11painful dysaesthesia with sometimes
42:12will use gabapentinoids like pre
42:15gabelein or gabapentin to help
42:17assist with at this stage as well.
42:19These drugs also are associated
42:21with genital eruptions as well as
42:23splinter hemorrhages on the nails.
42:25So we don't really have great treatments
42:27for the hand foot skin reaction right now.
42:30Unfortunately, many patients don't
42:31respond to moisturizers and karata lytic,
42:33or topical steroid ointments and
42:35so dose reduction is often needed.
42:37So we're doing a study looking at a
42:39novel topical nitroglycerin ointment
42:41to treat grade two or grade three
42:43hand foot skin rash and the first
42:45phase is going to be comparing it to
42:48vehicle and then the second phase.
42:50Comparing pyren lower percentages
42:51and so if you have any patients
42:53who present with hand foot skin.
42:56On these approved drugs on the left
42:58who have great to her Grade 3 and
43:00really most patients eventually get
43:02to grade 2 because it's almost always
43:04interfering with her activities
43:05of daily living.
43:06Please please I'll refer them to our study.
43:09We definitely need to do better
43:12in managing this toxicity.
43:14In interest of time,
43:15I'm just gonna I'm just just briefly
43:17highlight that we could spend all day
43:19talking about the different targeted
43:21agents in the toxicities I see.
43:23Here are some examples just to illustrate
43:25that really many different classes can do it.
43:27Since you were on or Brewton if for
43:29CLL often get perperek eruptions,
43:31folliculitis patients with breast
43:33cancer on PR, 3 kinase inhibitors,
43:34and get really terrible.
43:36Morbilliform exanthems some requiring
43:37the use of Prednisone so wanted to turn
43:39now to immune checkpoint inhibitors.
43:41Because I think you pennis
43:43toxicities are really important.
43:44To discuss with this class
43:46of cancer cancer therapy.
43:48And so all great rash,
43:49plus parictis it kind of tally.
43:51It all can occur in up to 50% of
43:54patients on checkpoint inhibitors at one
43:56point in time during their treatment.
43:58This is especially true of patients
44:00who are on combination CTL,
44:02a foreign PD one therapy and the way
44:04that I think about the toxicities
44:06from the checkpoint inhibitors is
44:07a categorized them into those that
44:10are the most frequent that we see
44:12which are the morbilliform rashes,
44:14the lichenoid rash,
44:15which I'll discuss a bit more about the
44:18exame and the parictis as well as psoriasis.
44:20And then there's the whole category
44:22of autoimmune disorders which occur
44:24as immune related adverse events such
44:26as diddle I go and bullous pemphigoid
44:28which I'll discuss more about as well.
44:30Fortunately, the severe rashes,
44:31the life threatening Stevens Johnson
44:32ones we've seen them,
44:34but they're not.
44:34They're not common,
44:35and then there's kind of the
44:37miscellaneous category of those that
44:39are granulomatis like sarcoid for those
44:42involving the panniculus or the fassia.
44:44So this is actually one of the
44:46largest studies out there.
44:47Looking at the different branches
44:48from in therapy that we published
44:50a couple of years ago and it was a
44:52retrospective retrospective study
44:53of over 100 rashes that we saw
44:55in the ankle during clinic and we
44:57found is that they really have many
44:59different clinical and histopathologic
45:00morphologies here and a lot of them
45:02resembled idiopathic dermatosis
45:03that that we treat in dermatology.
45:05For patients who are not
45:06on checkpoint inhibitors.
45:08If you take a look at the yellow box I
45:10highlighted kind of the top five and
45:12what's interesting about this is that
45:14a lot of these common rashes actually
45:16develop many months into therapy.
45:18The most common one can be sometimes
45:20six months into treatment,
45:21and I think that's important because
45:23patients don't always realize or
45:24put together that their new rashes
45:26because of their immune therapy,
45:27and in some of the oncologist who are
45:29less familiar with these toxicities,
45:31also may not.
45:32And so I I think that's important to
45:34keep in mind that you can definitely
45:36get late toxicities to write.
45:37This is a very prominent feature.
45:39In most of these containers,
45:41toxicities fortunately were able
45:42to manage these patients in the
45:44vast majority of time,
45:45topically by 20% of patients required
45:48Prednisone because of the severity
45:49of the rash and 25% had disruption
45:51of immune therapy at some point,
45:53sometimes before they saw me in clinic,
45:56or sometimes because the rash progressed.
45:58But really,
45:58the vast majority can remain
46:00on immune therapy.
46:01It was just the cases of Stevens Johnson,
46:04a really bad bullous pemphigoid where
46:06immune therapy was discontinued and another
46:08important concept here is for the rashes.
46:10That do recur after
46:11Prednisone or or that persist.
46:13Targeting the dermatosis in a more
46:15efficient way is probably going to
46:17be the future of how these rashes
46:19are treated and so we've had a great
46:21deal of success using things like
46:23asset reading for the psoriasis
46:24or lichenoid rash Om Alisme after
46:26methotrexate for the Bulls tend
46:28to glide and the TNF inhibitors
46:30for Stevens Johnson,
46:31which is how we treat it typically.
46:33More recently for for the cases that
46:35are not associated with checkpoint,
46:36I wanted to take a moment
46:39to discuss that the.
46:40What what the lichenoid dermatitis
46:41is we throw around the term lichenoid
46:44alot in dermatology and I'm not
46:45sure if the if our colleagues in
46:47meddock or familiar with it and
46:49so like in what looks like like in
46:51which an Organism that grows on
46:53trees kind of scaly and crusty looks
46:55kind of like the rash does.
46:57And then there's the histologic term
46:58of lichenoid dermatitis which is an
47:00interface dermatitis with the bandlike
47:01infiltrate of lymphocytes ANAN.
47:03This is the most common histopathologic
47:05finding that we see in the skin.
47:07And so the lichenoid rash can occur
47:09in up to a third quarter to 1/3 of
47:12patients on PD one and PD Wagon one agents.
47:15And this is kind of a more severe
47:17example highlighting the pink
47:19violaceous scaly patches and plaques.
47:21Here's a patient who responded to
47:23Acitretin were very persistent Palmer
47:25planter involvement and he did not
47:27do as well with topical steroids or
47:29even a short course of Prednisone.
47:31I also wanted to highlight that this
47:33lichenoid rash can involve the mucosa,
47:35and when that occurs,
47:36it can really be quite severe
47:38with ulcerations on the genitals
47:40as well as the oral mucosa.
47:42Anan this this this clearly is very
47:44painful and we were very low threshold
47:46for Prednisone in these cases.
47:48Sometimes we try things like
47:50hydroxychloroquine in those that persist.
47:52So in addition to the lichenoid
47:54rash from checkpoint inhibitors,
47:55we can also see eczematous presentations.
47:57Sorry, acid form presentations.
47:59And then there's patients that
48:00just have terrible parictis even
48:02without an associated rash.
48:03So here's a typical scenario
48:05of a patient with psoriasis,
48:06then goes on checkpoint
48:08inhibitor therapy and flares,
48:09and she responded very well to phototherapy,
48:11which is a really nice non
48:13systemic option for these patients.
48:15Here's an example of widespread eczema,
48:17and here's a patient that I share with
48:19Doctor Goldberg who just developed just
48:21severe itch and she comes to clinic,
48:23covered in bandages and
48:25explorations and she eventually.
48:26Did somewhat better with pre
48:28gabelein and phototherapy,
48:29so just highlighting that the different
48:31the spectrum of these papulosquamous
48:33rash as we call them from dermatology.
48:36So both paperboy is one of those
48:38rashes which is not common,
48:39but it's a very important one because
48:41it has a great deal of associated
48:43morbidity with it and so for those
48:46who aren't familiar with it,
48:47it's an autoimmune blistering
48:49disease with deposition of IG G and
48:51compliment at the dermal epidermal
48:52junction is seen here in my patients
48:54tissue sample and patients also
48:56make autoantibodies against BP 180,
48:58so we conducted a study a few years
49:00ago at our uncle during clinic
49:02and we found that about 1% of the
49:04patients on checkpoint inhibitors
49:06with PD one or PD wagon one.
49:08Based on our pharmacy develop
49:10this rash so it's not common,
49:12but but it definitely can be quite
49:14extensive and the latency is
49:16also usually four to six months.
49:18Clinically,
49:19patients will often present with
49:20just worsening queritis even before
49:22the onset of rash.
49:23Then they get these urticaria lesions
49:25with tense vesicles and bullae,
49:27which can become eroded,
49:28and you can also get mucosal
49:30involvement as well.
49:31Think about the bullous pemphigoid
49:33rash is unlike a lot of the more
49:36common exanthems and lichenoid rash.
49:37These typically require Prednisone due
49:39to the severity of the presentation
49:41with blisters.
49:42We've also had cases which have
49:44persisted even after immunotherapy
49:45has been stopped,
49:46and even after a Prednisone taper
49:48likely do too.
49:49I'm just immune activation and so
49:51for those cases things like Rituxan,
49:53MAB formalism,
49:53Maverick dupilumab which are biologics,
49:55I'll discuss later might be very helpful.
49:59And the one one question about that
50:01comes up a lot is when to worry about
50:04a typical macular papular example,
50:06when should you worry about progression
50:08of Stevens, Johnson, and so?
50:10My advice with these cases is obviously,
50:12you know,
50:13you can grade it based on the
50:15body surface area,
50:16but when the rash is pink and pure Riddick.
50:20It's very reassuring when the rash
50:22starts to become this more dusky color.
50:25And painful. That's when you really
50:27have to worry about a progression to
50:29a more severe cutaneous reaction,
50:31especially if there is any coastal
50:33involvement or blisters or any systemic signs
50:35or symptoms really have a low threshold
50:37for Prednisone and watching carefully,
50:39we've definitely seen these very
50:41atypical scenarios where an example
50:43just progressed and slowly over the
50:45course of several weeks progressed to
50:47a Stevens Johnson type of scenario.
50:49And that's been that's been
50:50published with checkpoint inhibitors,
50:52which is actually very different
50:53than classical Stevens.
50:54Johnson would just takes off.
50:56At a very rapid tempo nears examples
50:58of examples that we've seen,
50:59as well as Stevens Johnson from
51:01Hippie Niveau.
51:04An I think the future direction
51:06for it for treating these cutaneous
51:08toxicities is is looking at a more
51:10efficient way to shut them down.
51:12Basically treating the dermatosis
51:13in the most targeted approach.
51:15There's definitely a good amount
51:16of data suggesting that the
51:18use of systemic steroids is,
51:19in general, fine, inappropriate,
51:21and it has has not been shown
51:23to impair tumor response when
51:24treating cutaneous toxicities,
51:26but for those cases that
51:27are just recalcitrant,
51:28I think we're going to find
51:30the use of anti aisle 413 drugs
51:32like the pillow mab or anti Ige.
51:35He antibodies like oh Melissa
51:36Matthews more frequently.
51:37We already have plenty of biologics
51:39used in psoriasis and I think there
51:42is mounting data in case series of
51:44these being used for checkpoint rash
51:46as well as TNS for Stevens Johnson.
51:48Here's an example of a patient I
51:50share with Sarah Weiss who had bullous
51:53pemphigoid which kept flaring when
51:54we slowly taper the Prednisone.
51:56Eventually,
51:57with the concomitant administration
51:58of Melissa Map were able to get
52:01the patient off criticism.
52:03And so in the final moments,
52:05I just wanted to highlight it's
52:07not the forgotten child,
52:08because we see lots of toxicities
52:10from the cytotoxic drugs.
52:11But these I think you're probably
52:13more familiar with because they've
52:15been around for a long time,
52:17but definitely,
52:17alopecia mucositis are kind of
52:19your hallmark toxicities.
52:20Nail changes are really important
52:21and he's come up a lot to my clinic,
52:24specially young women with breast
52:26and gynecological cancers on
52:27taxanes or anthracyclines.
52:28They get very painful
52:29paronychia subungual hemorrhage.
52:30They can lose the nail plate they can become.
52:33Co infected,
52:34and so I think these toxicities are
52:36really important and then there's
52:38the toxic rash of chemotherapy
52:39which can be hand foot syndrome
52:42or malignant intertrigo flow under
52:43the umbrella of toxic erythema of
52:46chemo and these reactions occur
52:48through the ecrivain excretion of
52:50chemo in the skin of echoing glands.
52:53And we just wanted to do a brief
52:55shout out to my awesome research
52:57fellow who just matched into
52:59dermatology at Cornell.
53:00Rihanna and she was very interested
53:02in looking at the cutaneous toxicities
53:04in patients we've seen with skin
53:07of color which really make up a
53:09large proportion of our clinic.
53:11And while the diagnosis in general or
53:13similar to patients without skin of color,
53:15there's clearly a very prominent
53:17finding of hyperpigmentation,
53:18which is very bothersome and very,
53:20very prevalent after a rash
53:22are examples of that.
53:24Patients who get fatal,
53:25I go with darker skin.
53:26It's obviously a lot more noticeable,
53:28and then there's definitely a propensity
53:30for starring starring alopecia,
53:31but also just keloid scarring.
53:33Here's an example of a patient with a
53:35keloid overport site which responded
53:37well to injection of triamcinolone,
53:38so I think it's important to look
53:41at how these toxicities differ
53:43and in various populations.
53:45And in closing went to refer
53:47patients to our clinic.
53:48I think the short answer is anytime
53:50you need a hand, we're really,
53:52really happy to see these patients.
53:53It is a privilege definitely for rashes
53:55that are higher grade that are impacting
53:57quality of life or that are recalcitrant
53:59to kind of conservative management.
54:01And definitely anytime there's a red
54:03flag that I mentioned like skin pain,
54:05duskiness, blisters or plus definitely
54:07send those patients our way.
54:09So in conclusion, I hope you'll you'll
54:11see from this talk that cutaneous
54:13toxicities are not just common,
54:15but they're also really important in the
54:17overall management of cancer patients.
54:19Ann Ann.
54:20I hope that Dermot Earley dermatologic
54:22intervention can make a difference.
54:23Remember that the EGFR acne
54:25reform rash often starts.
54:26It is a sterile rash,
54:28but it can often be secondarily
54:30infected and you can get these unusual
54:32late perperek eruptions as well.
54:34Hand foot skin from the anti angiogenesis
54:37drugs and definitely have associated pain.
54:39We don't have great treatments yet,
54:41so please consider referring patients
54:42to the study using a novel nitroglycerin
54:44ointment to treat it and then turning
54:46to the checkpoint inhibitor rash.
54:48I think the lichenoid one is
54:50the important one to know about.
54:52It's common it can have associated
54:54parictis and mucosal involvement
54:55as well as bullous pemphigoid,
54:56which frequently requires systemic therapy.
54:58And if there's any red flag,
55:00signs or symptoms,
55:01obviously you know you have to
55:02treat these patients aggressively.
55:04So I just wanted to thank really all
55:06of my colleagues Ann and Metang.
55:09Sir John Cradoc,
55:10everyone at Smilow who's supported
55:11our clinic over the years.
55:13I have a really great team from the
55:15admins to the nurses to my chief residents,
55:18many of which have chosen Uncle Dharmas.
55:20Akarere Anatomy very proud and as well
55:22as my my research fellows, an NYCC I.
55:25So if you ever have any patients,
55:27I'm very I'm always available.
55:28You can text me call me.
55:30Contact us and we'll gladly see them.
55:33So thank you and I'll take any questions.
55:39It's terrific, thank you, Jonathan.
55:41Do you have questions from the audience?
55:54My recollection is that with the the
55:57B RAF inhibitors there was a serious
56:00problem with squamous cell carcinoma's is
56:02that yeah so
56:03actually had a.
56:04I had a picture of that slide.
56:07I didn't go into it too much but but we had.
56:11We saw a lot of toxicities over the
56:13years with the beer at inhibitors,
56:15but with the concomitant administration
56:17of the American hitters we've actually
56:19seen that basically drop down to
56:21near near 0 and so you can still get
56:23phototoxic rash is another odd things,
56:25like everything and awesome,
56:26we've not seen squamous cells
56:27develop in patients on be right
56:29contributors to the American hitter.
56:31Coadministration
56:31perfect thank you.
56:40Any other questions?
56:49If not, thank you Jonathan.
56:50Very interesting. Looks like
56:51you're making a lot of progress in
56:53managing these these disorders.
56:56Thanks for having me.