Together Against Melanoma: An Educational Symposium for Patients and Caregivers

Name: Together Against Melanoma: An Educational Symposium for Patients and Caregivers
Uploaded: 2026-05-14T12:50:45.43Z
Duration: 1 h 37 min 46 s
Description: May 12, 2026 Welcome: Kelly Olino, MD, FACS Speakers: Jonathan Leventhal, MD, Kelly Olino, MD, FACS, Thuy Tran, MD, PhD, Jeffrey Ishizuka, MD, PhD Panelists: Carla Beccera, PA; Lisa Fox, APRN, MSN; Sajid Khan, MD; David Schoenfeld, MD, PhD; Tormod Westvik, MD

May 14, 2026

May 12, 2026

Welcome: Kelly Olino, MD, FACS

Speakers: Jonathan Leventhal, MD, Kelly Olino, MD, FACS, Thuy Tran, MD, PhD, Jeffrey Ishizuka, MD, PhD

Panelists: Carla Beccera, PA; Lisa Fox, APRN, MSN; Sajid Khan, MD; David Schoenfeld, MD, PhD; Tormod Westvik, MD

About the speakers

Sajid A Khan, MD, FACS, FSSO
Associate Professor of Surgery (Oncology); Section Chief, Hepato-Pancreato-Biliary (HPB) and Mixed Tumors, Surgery; Co-Director of Team Science, Yale Center for Clinical Investigation (YCCI); Co-Program Leader, Advanced Hepatobiliary Disease, Yale Cancer Center
Jonathan Leventhal, MD
Associate Professor Term; Director of Residency Program, Dermatology; Director of Onco-Dermatology Clinic
Thuy Tran, MD, PhD
Assistant Professor of Medicine (Medical Oncology)
David Schoenfeld, MD, PhD
Assistant Professor of Medicine (Medical Oncology)
Kelly Olino, MD, FACS
Associate Professor Term; Leader, Skin Cancer Surgery, Melanoma Program; Clinical Director of the Smilow Melanoma Program, Yale Cancer Center; Co-Director Cutaneous Malignancy Tumor Board, Yale Cancer Center; Medical Student Clerkship Liaison for Division of Surgical Oncology, Surgery; Chair Credentials Committee and Secretary of Medical Staff, Surgery
Jeffrey Ishizuka, MD, DPhil
Assistant Professor
Tormod Westvik, MD
Associate Professor of Surgery

Information

ID: 14215
To Cite: DCA Citation Guide

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00:00Everyone?
00:02Everyone can hear okay in
00:03the back?
00:04Okay. Perfect. It's better than
00:06a Zoom call.
00:08So I just wanna thank
00:10every one of you who's
00:11come in the audience, many
00:13of whom we all know
00:14quite well.
00:16And it's always wonderful when
00:18people show up to support
00:20each other. And many of
00:21you have had very different
00:23journeys
00:24with us.
00:25We'll have time at the
00:26end for people to share,
00:28ask questions as well.
00:31You know, and tonight, I
00:32I think a lot of
00:33it is a night of
00:34celebration,
00:35for all of the things
00:37that have changed from the
00:38time that I was in
00:39training.
00:40I tell people all the
00:41time when I first started
00:43my journey,
00:44you know,
00:45as a family member of
00:47people who passed from melanoma,
00:49working on some of the
00:50things that won Nobel prizes
00:52and couldn't
00:54couldn't give it to a
00:55family member and where we've
00:56come
00:57in all of these years
00:59and that all of you,
01:01some of you who are
01:01in the audience were astronauts.
01:03You know, you
01:05there was a crazy ideas
01:07about immune therapy,
01:08and you guys went along
01:10for the ride. And not
01:11only that, but supported, you
01:13know, family members through the
01:15process.
01:16So on that note, thank
01:18you all. Debbie, I'm gonna
01:19you can
01:20make some opening remarks.
01:30Hello, everyone. I am Debbie
01:32Chergai. I am the senior
01:33education program manager at the
01:35MRF.
01:37We partnered today,
01:39with the ELF to put
01:40this symposium on for you
01:41today, so thank you so
01:42much for being here.
01:47First, I just wanna thank
01:48our sponsors.
01:50They these amazing companies have
01:52sponsored not only events like
01:54this, but they sponsor some
01:55of our other, many educational
01:57opportunities and events. In fact,
01:58if there's anyone here from
02:00any of these companies, is
02:01there, any industry reps here?
02:03Please raise your hands.
02:04Yes. Awesome. Take a look
02:06around. Thank them. Yes.
02:09Thank you so much
02:11for being here and for
02:12supporting events like this.
02:14Without their support, we truly
02:15could not do some things
02:17like this.
02:18First, I just wanna give
02:19a few facts.
02:21Some of you guys might
02:22know these already. In twenty
02:23twenty
02:24five, over two hundred and
02:26twelve thousand people. Oops. Sorry.
02:31There we go. People living
02:33in the United States are
02:34expected to be diagnosed with
02:35melanoma.
02:37Nearly ninety three percent of
02:38melanomas are thought to be
02:39caused by exposure to UV
02:41light and sunlight.
02:43Melanoma is not just a
02:44skin cancer, it develops anywhere
02:45in the body, eyes, nails,
02:47feet, mouth,
02:48and the five year survival
02:50rate for stage one to
02:51two localized melanoma is ninety
02:53seven point six percent.
02:55There are over one point
02:57four
02:57million people living with melanoma
02:59in the United States.
03:02And as I'm sure all
03:03of you know, melanoma is
03:04the deadliest form of skin
03:05cancer,
03:06and skin cancer is the
03:07most common form of cancer
03:09in the United States.
03:14The Melanoma Research Foundation is
03:16the largest independent organization
03:18devoted to melanoma,
03:20committed to the sport of
03:21medical research to develop effective
03:23treatments and eventually a cure
03:25for melanoma. I'm gonna give
03:26you just a short overview.
03:28I'll try to go quickly
03:29so we can get to
03:30the real amazing speakers today.
03:35This is our founder, Diana
03:36Ashby.
03:37She,
03:38MRF was founded in nineteen
03:40ninety six. She was diagnosed
03:41with melanoma and after a
03:43three year battle,
03:44found that there were no
03:45options for new therapies and
03:46clinical trials.
03:48A lot has changed since
03:49then.
03:52Diana's legacy lives through the
03:53MRF and all the incredible
03:55work we do. The MRF,
03:57we have three main, pillars,
03:59education, research, and advocacy.
04:01This is an example of
04:03one of our many educational
04:04events that we put on,
04:06and I'll go over just
04:07a few of the other
04:08things we have as well.
04:10A
04:11little bit of our footprint
04:12today. The MRF hosts several
04:14events all over the country
04:15including,
04:17nineteen,
04:19five k runs in different
04:20cities and states, two signature
04:22galas,
04:24and we bring patients and
04:25caregivers to DC
04:27to talk with congressional leaders
04:28about what is needed and
04:30why more funding is required
04:31for melanoma research.
04:36Research really is at the
04:37heart of our mission, supporting
04:39scientists whose discoveries lead to
04:41better treatments, improve outcomes, and
04:43new hope for melanoma patients.
04:46This slide highlights some of
04:47the groundbreaking research that MRF
04:49has funded in the past
04:50three in the past years
04:51and continues to support today.
04:53We have awarded thirty four
04:55grants,
04:56in two hundred and twenty
04:58five or sorry,
04:59twenty twenty five,
05:01and we've funded over twenty
05:02eight million dollars in research
05:04overall.
05:06This next slide,
05:09highlights some of the grants
05:10that we funded for Yale.
05:12So since two thousand eleven,
05:13the MRF has provided over
05:15nine hundred and fifty thousand
05:17dollars through nine grants
05:18to support the melanoma research
05:20at, at Yale. Through these
05:22grants, researchers
05:23have produced exciting results for
05:25the melanoma research community, including
05:28twelve
05:28scientific publications to advance the
05:31understanding of melanoma and its
05:32treatments.
05:34The MRF supported projects have
05:36also enabled Yale researchers to
05:38start over over forty new
05:40scientific collaborations and helped four
05:42Yale researchers
05:44secure additional funding from other
05:45sources to support their research.
05:52This is one of my
05:52favorite slides.
05:54Did you know that by
05:55funding melanoma research, you are
05:57also helping to advance
05:59all cancer research?
06:01Melanoma research breakthroughs have led
06:03to approvals in both targeted
06:04therapies for BRAF mutations
06:06and immunotherapy
06:08treatments
06:08for many cancers.
06:10Since the development of immunotherapy
06:12in the last ten years,
06:13distance
06:14metastatic disease patient survival rates
06:17increased
06:18from fifteen percent
06:19to over fifty percent.
06:21And as you can see
06:22in the slide, these are
06:23all the other,
06:25cancers that,
06:27you help by helping to
06:28fund melanoma research.
06:33Another facet of our research
06:34is our breakthrough consortium,
06:37which accelerates melanoma translational research
06:39through multi institutional collaborations and
06:42fostering the growth
06:44of early career scientists and
06:45clinical investigations.
06:47And as you can see,
06:48Yale University is on there.
06:52We have a variety of
06:53educational opportunities,
06:55not only directed at patients,
06:56but caregivers, providers.
06:58We have educational materials, webinars,
07:01animated patient videos,
07:03patient we give patient caregiver
07:04symposia like this, and we
07:06also have a lot of
07:07materials on rare subtypes.
07:11We have over thirty pieces
07:13of literature available on our
07:15website these are all free
07:17to download or order you
07:19can order bundles of them
07:20so if you have an
07:21educational event that you want,
07:24to bring some information to,
07:26I highly suggest
07:27going on our website, checking
07:29out our educational literature page,
07:30at the very end there's
07:31an order form,
07:33and you can order
07:34five hundred up to five
07:36hundred different types of or
07:37five hundred,
07:38materials
07:39for your events all for
07:41free.
07:42And you could do it
07:43multiple times a year.
07:49The melanoma the MRF also
07:51hosts monthly ask expert webinars.
07:54We have animated patient videos.
07:57These are great videos that
07:58are very short. They're about
08:00all less than ten minutes.
08:01They're a great way to
08:02share with people if you
08:04wanna educate them on, some
08:05of the,
08:06parts of melanoma,
08:08and we have some new
08:09ones in the
08:10works. And then also,
08:12if you want more education
08:13on our MRF YouTube channel,
08:16you can find all of
08:16our past patient and caregiver
08:18symposia. The one today will
08:19also be posted there in
08:21a week or two.
08:22All of our past, ASSA
08:24expert webinars, patient testimonials,
08:27and tons of other other
08:28things if you're looking for
08:29some more education.
08:32We also have an amazing
08:34patient and caregiver community.
08:36This, has been going on
08:37for many, many years, and
08:38so you can find so
08:39many different topics such as
08:41Till cell therapy, you know,
08:43new therapies,
08:44newly diagnosed patients who want
08:46some questions answered, bereavement
08:48support,
08:49there's so many different topics
08:51that you can search or
08:52you can start your own
08:53conversation.
08:57This is our new, program
08:59it's called SunAware.
09:00It's a sun safety e
09:02learning program for children in
09:03grades k through five.
09:05This curriculum promotes healthy sun
09:07safe habits to help prevent
09:09melanoma, skin cancer, and sun
09:10related skin damage.
09:12Right now, we are,
09:16circulating it through schools,
09:18and also youth organizations.
09:20If you guys want more
09:22information on it, for any
09:23of your local communities, please
09:25give us a contact.
09:30As I mentioned before every
09:31year we bring caregivers to
09:33the hill patients and caregivers
09:34to the hill to meet
09:35with state legislators and congressional
09:38leaders.
09:39We work with them to
09:40help increase funding for cancer
09:41and specifically melanoma research.
09:44If you would like to
09:45attend any of our, advocacy
09:47days, please contact us and
09:49we'll let you we'll let
09:50you know when the next
09:51one is.
09:54We have several prevention and
09:55awareness campaigns, included our get
09:57naked, I get dilated,
10:00Stay,
10:01Spot Stay Safe with Spot
10:03campaign with for pediatric melanoma
10:05awareness.
10:06Our twenty twenty six spokesperson
10:08is Jason Chambers. I don't
10:09know if any of you
10:10recognize him. He is a
10:12melanoma patient, superyacht captain in
10:15bravo below deck,
10:18down under star, and he
10:19is our new spokesperson this
10:21year.
10:24We also have several programs,
10:26that you can find more
10:27about on our website.
10:31And there are several opportunities
10:33if you're looking for ways
10:34to get involved. We have
10:35community fundraisers, galas, miles for
10:37melanoma walks. There there was
10:39a postcard for,
10:41a local one going on
10:43soon if you guys, on
10:44our table, if you're interested
10:46in attending.
10:49And lastly, the best way
10:50to learn more about anything
10:51that I mentioned here, any
10:52events that we have coming
10:53up, or anything in the
10:54future is to just follow
10:56us on social media. We're
10:57on on the major,
10:58channels.
11:02In your folders today or
11:04with your folders today, we
11:05also gave you a post
11:06event survey.
11:08There's also a QR code
11:10that you can scan at
11:11the MRF table. We would
11:12really appreciate you filling out
11:14this survey. You can fill
11:15it out today as you
11:16go along or you can
11:17do it and hand it
11:18to me as you leave
11:19or you can do it
11:20online later. We'll follow-up with
11:21an email with a link
11:22to the survey as well.
11:24It's a very short survey,
11:25but I promise you it's
11:27really important. It lets us
11:28know,
11:29you know, topics that you
11:31wanna hear more about, and
11:32it helps us create more
11:34events that are important to
11:35you.
11:38Lastly, I just wanna thank
11:39the sponsors again,
11:40for supporting events like this
11:42and for being here.
11:43And, of course, Yale New
11:45Haven Health, thank you so
11:46much for partnering with us
11:48today.
11:57So, before we actually start,
12:01with the the physicians here
12:03to give information, we actually
12:05wanted to have one of
12:06our patients who's had
12:08really quite the incredible journey.
12:11And if you wanna
12:14yep.
12:16Where do you want? You
12:16can go wherever you want.
12:18You're the star of the
12:19show.
12:20But come up here. Do
12:21you want a microphone and
12:22sit? Where'd you be comfortable?
12:23Okay. Here.
12:25Probably.
12:26Alright.
12:30And it's on. Okay. If
12:31it becomes too loud,
12:33just give me a signal.
12:35My name is Brandy Orton.
12:36I am,
12:38I'm married. I'm a mother
12:39of two children ages twelve
12:40and thirteen.
12:41My
12:42I have or had melanoma.
12:45Date my story dates back
12:46to
12:48people can't hear you? Okay.
12:49Okay. Is that better? Okay.
12:51Brandy Wharton,
12:53married, mother of two children.
12:54My melanoma story goes back
12:56to twenty nineteen, twenty twenty.
12:58I found a cut on
12:59my wrist, and what popped
13:00up a couple weeks later
13:01was something that looked almost
13:03like, a blister you get
13:04on the back of your
13:05heel. And at this point,
13:06I was forty years old.
13:07I'd had over thirty two
13:08basal cell carcinomas and several
13:10squamous cells. So I was
13:11very familiar
13:13with the dermatologist.
13:15I asked the dermatologist about
13:16that, and they said it
13:17was nothing, and then COVID
13:18hit. So I didn't go
13:19back to the dermatologist
13:21again until after the the
13:23majority of COVID had passed.
13:25When I did return, I'd
13:26asked about the spot again
13:27because it continued to grow,
13:28and they again told me
13:29it was nothing to worry
13:30about. They tried freezing it,
13:32and it grew very quickly.
13:33And, eventually, I had a
13:35biopsy and learned that it
13:36was melanoma.
13:37And in fact, I was
13:38told they believed it was
13:39a secondary cancer that, there
13:41was another type of cancer
13:42in my body. And during
13:43that time, I had over
13:44a month to wait for
13:45scans, so I really delved
13:46into a lot of I
13:48grew up in a natural
13:49focused household, so I dove
13:50into some of the research
13:52on naturopathic care and things
13:53I could do at home.
13:55We shifted to an organic
13:56diet and started juicing and
13:57taking some supplements.
13:59And then I found that
14:00the cancer luckily was not
14:01anywhere else in my body.
14:02I had a wide margin
14:03excision, and I thought that
14:04I was good to go
14:06and safe. I am an
14:07active duty service member, so
14:08I executed orders, and we
14:10moved to Tampa. And as
14:11part of my follow on
14:12care, we learned just a
14:13few months later that the
14:14cancer had, in fact, spread
14:16to the lymph nodes in
14:17my elbow.
14:18And so I met with
14:19the surgeon and with the
14:21oncologist,
14:22and I had a lot
14:22of questions. I'd done a
14:23lot of research. I had
14:24two young kids. I was
14:26very scared, and a lot
14:27of my questions were just
14:28brushed off. I felt unheard.
14:30I was told, hey. If
14:31you don't get treatment, you're
14:32gonna die, and they never
14:33answered my questions.
14:34I'd asked for a printout.
14:37They told me about the
14:38side effects of the treatment
14:39and statistics, and I was
14:41given a two page handout.
14:42And I left the doctor
14:43feeling very
14:45unfulfilled and very frustrated,
14:47and I thought there had
14:48to be a better way.
14:49So what it followed was
14:50a four year kind of
14:51journey where I tried a
14:52number of naturopathic things. I
14:54tried hyperbaric oxygen. I tried
14:55colon hydrotherapy. I tried lymphatic
14:57massage. I tried a number
14:59of diets and supplements, IVs,
15:01infrared saunas. But, ultimately, over
15:03the next four years, my
15:04cancer continued to grow until
15:06about September of twenty twenty
15:08four.
15:09I got follow on scans
15:10that showed it had spread
15:11to the lymph nodes in
15:12my in my, armpit, the
15:14axillary lobe. And I knew
15:16that that was a jumping
15:16off place to spread to
15:17other organs. And I was
15:18extremely scared because I was
15:20a, you know, a mother
15:22of two,
15:23with a wonderful career and
15:25a wonderful family, and I
15:26just was scared. I didn't
15:27know what to do, but
15:28I had been very frustrated
15:29by the interactions I'd had
15:31with the doctors up to
15:31that point. All of my
15:33concerns seemed to be brushed
15:34off,
15:35and none of my questions
15:36were answered. And I wasn't
15:37smart enough. I knew I
15:38wasn't smart enough to understand
15:40the medical,
15:41documents that I was reading.
15:43And so I felt very
15:44frustrated and kinda like I
15:45had nowhere to go.
15:46And, ultimately, I got a
15:48referral to Yale, and I
15:50met these two wonderful ladies.
15:51I met doctor Olena and
15:52doctor Kluger.
15:53And I will tell you
15:54that my experience was different
15:55at the get go.
15:57I got a call from
15:58nurse Rachel. She spent about
16:00thirty to forty five minutes
16:01on the phone asking me
16:02what had brought me here.
16:04I'd never had that before.
16:06I really felt heard, and
16:07I felt hopeful.
16:08And I went into the
16:10interactions with the doctors with
16:11a different kind of mindset
16:13just based off of that
16:14interaction.
16:15And then I met doctor
16:16Kluger, and I had a
16:17number of questions. And I
16:18actually warned nurse Rachel, like,
16:19hey. I ask a lot
16:20of questions. It's not because
16:21I'm trying to be I'm
16:22not trying to quiz the
16:23doctors. I'm genuinely curious. My
16:25life is at stake.
16:27I have questions that I
16:28need answered, and she welcomed
16:29the questions. And doctor Kluger
16:31answered every single one of
16:32those questions. Because at the
16:33same time as I was
16:34going through all these naturopathic,
16:36practices, I was still dialing
16:38into the AIM melanoma foundations,
16:40clinics that they would hold.
16:42I was keeping track of
16:43the research and trying to
16:44understand the studies that were
16:45coming out.
16:46And doctor Kluger was phenomenal.
16:48She answered every single one
16:49of my questions and was
16:50able to tell me why
16:51a certain,
16:52procedure or a certain treatment
16:54was not the ideal one
16:55for me or the additional
16:56risk that I held. And
16:57doctor Olena was wonderful. She
16:59came in, and she was
17:00very frank with me about
17:01the surgery and the potential
17:02side effects,
17:04but she was also very
17:04hopeful. And I left that
17:06doctor's appointment for the first
17:08time. I didn't cry leaving
17:09a doctor's appointment because usually
17:10I would I would have
17:11such anxiety and have such
17:12a bad experience that I'd
17:14be shaky and I would
17:15cry, and I left feeling
17:16hopeful.
17:18And that in conjunction with
17:19actually getting the full pamphlet
17:20of information,
17:22I read through it. I
17:23understood all the side effects.
17:24I felt fully informed enough
17:26to make a decision for
17:27my treatment for the first
17:28time, and that it's, you
17:29know, stemmed back to when
17:30I first learned I had
17:31cancer in January of twenty
17:33twenty one.
17:34That was incredible for me.
17:35That was a life changing
17:36experience.
17:37So I started immunotherapy.
17:39I had the double dose
17:40treatment.
17:41It started in November. We
17:42had planned a family trip
17:44to, Germany because it was
17:45my lifelong dream, and we
17:46weren't sure how much time
17:47I had because I was
17:48in pretty bad shape.
17:49We went to Germany. It
17:50was a rough trip,
17:52but I'm glad I went.
17:53And about a week before
17:54the second treatment,
17:56I was like, hey. I
17:57said to my husband, I
17:57think my tumor is shrinking.
17:59And he's like, yeah. Of
18:00course, it's shrinking. You know?
18:01He always had a positive
18:02mindset. He was always trying
18:03to be my cheerleader. And
18:05then, actually, the kind of
18:06reaffirming thing is my teenage
18:07daughter said, hey, mom. I
18:08think your tumor is smaller.
18:09And she hadn't heard me
18:10say anything, so I knew
18:11that, like, something was going
18:12on. And with that, no
18:14matter the side effects that
18:15I was experiencing, I was
18:16so hopeful. I was like,
18:17I can experience any side
18:18effects, and I will get
18:19through this because I'm seeing
18:20results.
18:21For the first time, I'm
18:22seeing results, and I just
18:24had such hope.
18:25So I did three doses
18:26of the double, double treatment.
18:29And then the decision was
18:30made by doctor Olino and
18:31doctor Kluger that it was
18:32time for surgery.
18:34I had surgery. And then
18:35a little while after my
18:36surgery, I learned that I
18:37had something called, I think,
18:38a complete response. Correct me
18:39if I'm wrong. Right? So
18:41my tumor had shrunk drastically,
18:43but what was what had
18:44remained had been completely killed
18:46by the treatments.
18:47I've continued with the single
18:49dose treatments,
18:50for good measure and because
18:51I did have some some,
18:52you know, enlargement in the
18:54lymph nodes up here. And,
18:56today, I had my second
18:57to last,
18:58immunotherapy treatment, and then I
19:00will be being monitored from
19:02here. So I just wanna
19:03say,
19:05I'm I'm thankful for my
19:07journey. I'm thankful for the
19:08things that I did to
19:09improve my overall health because
19:10I think they helped, you
19:11know, strengthen my immune system
19:13and set me up well
19:14for the surgery and the
19:15treatments that followed. But I
19:16am so extremely thankful for
19:18doctor Kluger
19:19and for doctor Olino
19:21for meeting me where I
19:22was at. And every patient
19:23is different. We all have
19:24our own journey, and we
19:25all need different things.
19:27I went to law school.
19:29I'm in the military. I'm
19:30trained to read everything to,
19:31you know, think critically, advise
19:33commanders on risk. So for
19:34me, I needed all the
19:36information to feel like I
19:37could make a well informed
19:38decision before I was comfortable.
19:40Some patients maybe don't need
19:41that. They don't wanna know
19:42because maybe it'll bring down
19:43their, you know, their mindset.
19:44They'll get scared, and they
19:45don't wanna know, and they
19:46just want that. And I
19:47was just so thankful that
19:48I finally found doctors who
19:49were able to meet me
19:50where I was at and
19:51make me feel comfortable enough
19:53to get the treatment that
19:53I needed. And I'm so
19:55incredibly hopeful for now the
19:57long life that I have
19:57ahead of me. Whereas less
19:59than six months ago, we
20:00were planning a final trip
20:01because we weren't sure if
20:02I was gonna make it.
20:03So thank you very much.
20:20That that I have a
20:21collection of that interaction for
20:23something completely different. See,
20:26I saw a lit you're
20:27a lieutenant. What's your rank?
20:28Walk into my office and
20:30tell me what was gonna
20:31happen. I didn't see an
20:32anxious lady who was nervous.
20:35Andy, I guess we just
20:36have a different read on
20:37that reality.
20:38Okay.
20:40That's why the surgeon got
20:42along really well with the
20:43military.
20:48Poor doctor Levinthal now has
20:50the unenviable
20:53to follow with this.
21:00Wow. I mean, that's really
21:01an inspiring story, and, thank
21:03you for sharing. And that's
21:04why we love what we
21:05do and being on our
21:06team here. So I'm John
21:08Leventhal. I'm a dermatologist at
21:10Smilo. I lead the Oncoderma
21:12Clinic. So I'm gonna get
21:13us started by going over
21:14many things that you probably
21:15already know, the diagnosis, risk
21:17factors, prevention, and screening of
21:19melanoma.
21:20You already heard a few
21:21key facts earlier, but skin
21:22cancer is the number one
21:24cancer in the United States.
21:26Melanoma is the fifth most
21:27common. And while basal cell
21:29and squamous account for the
21:30majority, melanoma is the deadliest
21:32form
21:33and,
21:34over a million people live
21:35with it, and we see
21:36it every day. So what
21:37is melanoma? Melanoma is specifically
21:39a tumor, a cancer of
21:41the cells that give our
21:42body pigment. Those are called
21:43melanocytes.
21:45And most cases occur on
21:46the skin in areas that
21:48are completely normal and then
21:49just develop. Some melanomas occur
21:52from an atypical birthmark or
21:54a mole that changes over
21:55time.
21:56So who develops melanoma?
21:58Anyone can develop melanoma. I
22:00have patients who are young,
22:02over a hundred, all genders,
22:04ethnicities.
22:05The majority of people statistically
22:07are older white men over
22:09age fifty. Under age fifty,
22:11more women than men tend
22:12to have melanoma probably due
22:14to tanning habits, but by
22:15age
22:16sixty five plus, more men
22:17have it than women.
22:18And as you can see
22:19in this chart, it's really
22:21incredible. The lifetime risk in
22:22the United States has dramatically
22:24increased over the past decades.
22:26And currently, it's probably about
22:28one in,
22:29probably,
22:30forty has happened in two
22:32thousand twenty six.
22:33So let's go over melanoma.
22:35So
22:36what do we do to
22:37diagnose it? So step one
22:38and the most important step,
22:39well, some of these
22:41slides aren't coming out, but
22:42that's okay, is identifying
22:44a concerning lesion, and that's
22:46really the most important step
22:47here. So we have to
22:48know what does melanoma
22:50look like.
22:52So it's very important to
22:53go over the a, b,
22:54c, d, e's. You're You're
22:55probably familiar with it. A,
22:56asymmetrical.
22:58B, the border's irregular. C,
23:00the color is varied.
23:01D, I don't like diameter
23:03pencil tip eraser because I've
23:04diagnosed some teeny tiny melanomas.
23:06So I prefer dark because
23:08the vast majority of melanomas
23:09that I find are dark.
23:11Not not all of them,
23:11but most of them. And
23:13e is probably the most
23:14important one, and that's evolution.
23:16So the lesion
23:17changes in any way, and
23:18patients are really good at
23:20coming in and saying, you
23:21know, doc? Something's a little
23:22bit different about this mole.
23:23And trusting that patient intuition
23:25is really key.
23:27And so what do melanomas
23:28look like? So the superficial
23:30spreading, these are the most
23:31common types of melanomas. They're
23:33atypical pigmented lesions. You can
23:35see these are some really
23:36classic ones that are pretty
23:37tough to miss. Right? They
23:38really obey all the a,
23:40b, c, d, e rules.
23:41Nodular melanomas,
23:43this is a kind of
23:44an aggressive type. They grow
23:45fast. Patients will come in
23:47and say, this thing just
23:48showed up a few months
23:49ago. It's growing really fast.
23:50These are the ones that
23:52you can't just wait for
23:53your yearly dermatology visit because
23:55you're gonna come in with
23:56a thick melanoma.
23:57Lentigo maligna, we see these
23:59in mostly elderly patients with
24:01lots of lentigos. Those are
24:02sunspots, and these melanomas arise
24:04in these in these chronic
24:06sun damaged areas. Now amelanotic,
24:08this is always a tough
24:10one. And I have a
24:10lot of patients that will
24:11come in and say,
24:12my dermatologist,
24:14you know, before seeing you
24:15thought it was a pimple.
24:16It was pink. It wasn't
24:17dark. They thought it was
24:18a basal cell. So these
24:20are not the most common
24:21presentations, but we see these.
24:23So this is kind of
24:23the rule I was mentioning
24:24earlier. If there's something on
24:26your skin that's changing, evolving,
24:27just doesn't seem right to
24:28you, a sore that's not
24:29healing, you should see a
24:30dermatologist.
24:31And then there's the melanomas
24:33that don't happen in areas
24:34with sun. They happen on
24:35the palms, the soles, under
24:37the nails. These are called
24:38aqual indigenous, and we see
24:40these predominantly in patients with
24:42darker skin types, but not
24:43always. The nail band melanoma,
24:46it it starts in the
24:47nail matrix, and it grows
24:49upward like a black band.
24:50So many of my patients,
24:52after seeing this talk, come
24:53in with a little blood
24:54spot under their nail and
24:55say, doc, I have melanoma.
24:56No. So not like a
24:57little red streak of blood,
24:58but a dark pigmented lesion
25:00that's a band in the
25:01nail fold.
25:02So
25:03what do we do next?
25:04We we obtain a skin
25:05biopsy. That's step two. And
25:07this is really easy for
25:08dermatologists to do. I could
25:10do it in thirty seconds
25:11probably. It just takes a
25:12couple minutes. And the type
25:14of biopsy is really not
25:15that important. Most of the
25:16time, we do a shave
25:17biopsy. But the important thing
25:19is having it read by
25:20a good pathologist. We have
25:21the best pathologist in the
25:22world here at Yale, and
25:24they're able to make the
25:25diagnosis.
25:26And the pathologist will also
25:27tell you how thick the
25:28melanoma tumor is, which is
25:30such an important,
25:31determinant
25:33of how of of survival
25:35prognosis.
25:36Majority of melanomas are thin
25:38stage one. Patients have, you
25:39know, close to ninety nine
25:40percent survival, good outcomes.
25:43So let's keep moving. So
25:44next is risk factors and
25:46prevention.
25:47So like any cancer,
25:49melanoma has,
25:50risk factors that are environmental,
25:53that we can modify, and
25:54has risk factors that are
25:55genetic
25:56and that we cannot, prevent.
25:59Sorry some of these slides
26:00didn't come out when, I
26:01sent the email. So this
26:03slide is showing you, you
26:05can guess what's in the
26:05middle, ultraviolet radiation from the
26:07sun. So that's the number
26:09one risk factor. So ultraviolet
26:11radiation hits the Earth's surface.
26:13Ultraviolet c is pretty much
26:14blocked by the ozone, but
26:16UVA and UVB penetrate the
26:18Earth's surface. UVA can also
26:20penetrate car glass windows. And
26:22what happens is these ultraviolet
26:23rays from the sun cause
26:25damage in our DNA in
26:26the skin, and as the
26:28DNA damage mutations,
26:30over time,
26:32develop,
26:33skin cancer
26:35forms. And, unfortunately,
26:36the type of ultraviolet exposure
26:38that is
26:40the most detrimental
26:41is the type we love
26:42the most. You know, sunny
26:44vacations at the beach, short,
26:45intense bursts of ultraviolet. And
26:48the majority of melanomas are
26:50attributed to to,
26:51ultraviolet radiation.
26:53And we know that sunburns
26:54in childhood matter a lot,
26:56but it's really the data
26:57shows it's cumulative sunburns. I
26:59have many patients that say,
27:00doc, I'm probably already in
27:02trouble. I burned a lot.
27:03I should just live out
27:04my life and enjoy myself
27:05in the sun. I say,
27:06yes. Your childhood sunburns hurt
27:08you, but we know from
27:09the data it's really cumulative
27:11sun damage. So you can
27:13reduce the total burden of
27:14ultraviolet damage. You can reduce
27:16the future risk of developing
27:18melanoma.
27:18We also know that tanning
27:20beds are a major risk
27:22factor.
27:22Studies have shown that young
27:24women in particular,
27:26they did a study, had
27:27a six fold increased risk
27:28of developing melanoma. In Connecticut,
27:30it's actually banned now, indoor
27:31tanning for minors. Many states,
27:34minors can still do indoor
27:35tanning beds.
27:36A question I get asked
27:37a lot. What about spray
27:38tan? Is that gonna cause
27:40melanoma?
27:40So spray tanning is okay.
27:42You just don't wanna overdo
27:43it and look like a
27:44carrot, like Ross from Friends.
27:46But spray tanning is fine.
27:48So let's go over the
27:49risk factors that we,
27:51can change. These are these
27:52are the genetic risk factors.
27:53And, again, my apologies about
27:55the slides, but having over
27:57a hundred moles is a
27:58risk factor. Having atypical moles,
28:01having lots of sunspots, all
28:03of these are risk factors
28:04for developing melanoma.
28:05And you can see the
28:06difference between,
28:08skin that has never seen
28:09the sun
28:10versus skin that has seen
28:11the sun underneath, all these,
28:13sunspots and formation of, these
28:15these these lentigels, we call
28:17them. We also know that
28:18having light skin, light hair,
28:20blue eyes, freckles, all of
28:21that increases a risk of
28:22melanoma.
28:23And a lot of our
28:24patients with melanoma have these
28:25risk factors.
28:26So if you look in
28:27the mirror and if you
28:28look a little bit like
28:29Julianne Moore, which is a
28:30great thing, you should be
28:31ultra, you know, protective of
28:32yourself in the sun.
28:34And then there's genetics, and
28:35we can change our genetics.
28:37Right? But it's important to
28:38know about it. If you've
28:39had a skin cancer, you
28:41have an increased risk of
28:41getting melanoma. You have a
28:43forty percent lifetime risk of
28:44getting another skin cancer if
28:46you've had a melanoma. If
28:47you have a first degree
28:48relative with melanoma,
28:49it doubles your risk. And
28:51we know that there's genetic
28:52syndromes, and I have some
28:53of these patients in my
28:54practice
28:55where genes get passed on
28:56from generation to generation, and
28:58there's a very strong family
28:59history of melanoma
29:00and other cancers like pancreatic
29:02cancer. And so I always
29:03go by the rule of
29:04threes. If you've had three
29:06melanomas personally
29:07or if you know three
29:08first degree relatives in your
29:10family that had melanoma or
29:11pancreatic,
29:12ask your doctor about genetic
29:14testing.
29:17And then finally,
29:18prevention.
29:19So we know ultraviolet radiation
29:21is the number one modifiable
29:22risk factor. Right? So avoid
29:24tanning, protect yourself in the
29:25sun. I get asked a
29:27thousand times a day, well,
29:28what sunscreen should I use?
29:29My patients bring in, like,
29:30twenty of them, and they're
29:31so concerned with which one
29:32to use. They're not using
29:33any of them. And I
29:34say, we need to simplify
29:35this. Okay?
29:37The best sunscreen is the
29:38one that you're gonna use.
29:40SPF thirty and above, the
29:41data shows that's really probably
29:43the number you need. Anything
29:45above that, like SPF a
29:46hundred, is much more expensive
29:47and probably doesn't give you
29:48a whole lot more benefit.
29:49But SPF thirty and above,
29:51that's what you're aiming for.
29:52Reapplying it every few hours
29:54when you're outdoors. I mean,
29:55that's really the big thing.
29:56Wearing a hat, sun protective
29:58clothing, and just using common
30:00sense. You can still enjoy
30:01your summer, but you should
30:02protect your skin. Then the
30:04last part of the talk
30:05are what can dermatologists do,
30:07and is screening important?
30:10So the United States Preventative
30:11Services Task Force, they say
30:13that not everyone on the
30:14planet needs a dermatologist
30:16for skin cancer screening.
30:18There's too many people. And
30:19so what we do is
30:21we don't recommend that everyone
30:22should be screened. But if
30:24you are an at risk
30:25individual, then you should. If
30:26you've had skin cancer before,
30:28if if you have a
30:28strong family history, if you
30:30look in the mirror and
30:31you're covered in atypical moles
30:32and hundreds of moles, you're
30:33someone who should see a
30:34dermatologist.
30:36Definitely see a dermatologist who's
30:37gonna do a thorough total
30:38body skin exam.
30:40Does not take a long
30:41time, but you can still
30:42be very thorough in a
30:43short amount of time. A
30:44dermatologist that looks at you
30:45from across the room is
30:46not the one that you
30:47should be seeing for a
30:48skin check.
30:49And youth education programs like
30:52we spoke about earlier, really
30:53important.
30:54And so the evidence has
30:56shown that dermatologists
30:57find melanoma tumors that are
30:59thin, thinner than the general
31:00population, thinner than primary care
31:02doctors, and so we know
31:03the thickness is super important.
31:05Picking up a thin melanoma
31:07earlier on is crucial. And
31:09we also know from studies
31:10that patients can be taught
31:11what to look for, doing
31:12skin checks, looking in the
31:14mirror every month or so.
31:15And so I always like
31:16to tell patients, look for
31:18the ugly duckling sign. Look
31:19for something on your skin
31:20that's different
31:22from other moles, changing. That's
31:24something you should bring to
31:25my attention. Don't wait if
31:26it develops a month after
31:27hour visit for our yearly
31:29skin check.
31:31What can we use as
31:32dermatologists? So we have certain
31:33tools.
31:34My patients know I don't
31:35I don't go anywhere without
31:36my dermatoscope, my dermlight. It's
31:38a magnifying lens. It allows
31:40us to look at them
31:40all, which should the naked
31:41eye might seem okay. But
31:43then with my dermlight, I
31:44might see some pigment changes
31:45that are abnormal, so I'll
31:47take a skin biopsy. So
31:48we all use dermatoscope.
31:50We sometimes do digital photography.
31:52I have some patients that
31:53are covered in atypical moles.
31:54We'll take photos and look
31:55over time. I still think
31:57the patient doctor interaction is
31:59more important than some new
32:01AI tool saying that something
32:03may have changed because some
32:04changes are okay.
32:06And then finally, I'll end
32:07by saying,
32:09advocate for yourself and your
32:10skin. Do do monthly or
32:11every couple months skin checks
32:13on yourself or your partners.
32:14All you need is a
32:16mirror and a handheld mirror,
32:17and I have a little
32:18demonstration here.
32:20Let's
32:23see.
32:33But it's can't like it.
32:45Look in the scalp,
32:47try to spread the toes,
32:49gotta look in the buttock,
32:51look in the areas,
32:53look in the sun, look
32:55in the mouth to purr
32:55on the back.
33:00So a nice thorough skin
33:01exam. So with that, I'll
33:02end, and I look forward
33:03to taking questions later. Thank
33:05you.
33:19Just a little shorter than
33:20doctor Leventhal.
33:23So I'm gonna talk about
33:24something that's been a real
33:25paradigm
33:26shift pretty much in the
33:27last five years and really,
33:28you know, highlights,
33:30the journey that that Brandy
33:31spoke a little bit about,
33:32and and that's the the
33:33shift towards what we call
33:34neoadjuvant
33:35therapy.
33:37So, again, historically, we talk
33:39about removing the skin, removing
33:42lymph nodes. Some of you
33:43may have had what we
33:44call a wide local excision
33:45and a sentinel node biopsy
33:46that are in the audience.
33:49But,
33:50you know, unfortunately, melanoma could
33:52spread to other locations. And,
33:54again, in the time before
33:55we had immune therapy,
33:58people sometimes had locations surgeons
34:00could remove and some of
34:01them did very well and
34:02others didn't have that same
34:04outcome.
34:06And again, here, lymph nodes,
34:08lots of people did pretty
34:09well. Lung, not so well.
34:11Other places.
34:12Right? This is again where
34:13we started from when we
34:15had hopes and prayers and
34:16surgery and not much else.
34:18And then again, many of
34:20you in the room may
34:20have received or have now
34:22heard about
34:23what was
34:24practice changing, Nobel Prize winning
34:27work,
34:29that
34:30came into clinical trials. And
34:32melanoma was one of the
34:33first fields
34:34actually to study this and
34:37patients, again, some of you
34:38that are even in the
34:38audience today, some of the
34:39first people who received this,
34:41actually received it at Yale.
34:45And with this, people again,
34:46the old paradigm was
34:48after surgery. So, again, someone
34:50would show up. They'd have
34:51tumors in locations. We take
34:53them out, particularly if they
34:54were in the lymph nodes,
34:55and then we would give
34:56people immune therapy. And people
34:58started saying this. Is this
35:00the best way to go
35:01about this? You know, scientifically,
35:03does this make
35:04sense?
35:05Right? So, you know, as
35:06with everything, we want to
35:07say, what are we doing?
35:09This has been successful, but
35:11how can we improve upon
35:12it? How can we learn
35:13more? How can we do
35:14better?
35:16So
35:17again, particularly in patients who
35:19had melanoma that we could
35:21feel, you know, areas in
35:23the the lymph nodes,
35:25places that we could see,
35:26areas in the skin, we
35:27call those in transits.
35:29And then also certain places
35:30where you could remove something
35:32with an operation, but maybe
35:34it wasn't an emergency.
35:35Sometimes a spot in the
35:36lung, a spot in the
35:37bowel.
35:39And
35:40why did we think that?
35:41Again, if you kind of
35:42think, you know, like a
35:43scientist and a doctor, you
35:45know.
35:46But again, a lot of
35:47common sense. If you have
35:48something in place and you
35:49give someone a treatment,
35:51you can kind of see
35:52what it's how it's working.
35:53Right? It shrinks.
35:54You know, Brandy had that
35:56experience.
35:57Sometimes, again, when it shrinks,
35:58it makes your operation
36:00safer to do. So if
36:01it works, you know, that's
36:02a good reason to do
36:03this.
36:04If we look at our
36:05immune system,
36:06again, if the target's in
36:08place, there's some thought that
36:09maybe we get a better
36:10variety of t cells that
36:12are surrounding the tumor that
36:14may persist longer even after
36:16the tumor is removed.
36:19And, again, for learning for
36:21the next patient, you know,
36:22for the next trial too,
36:24we learn every single time
36:25that we have a response
36:27or we don't have a
36:28response
36:29from our patients and from
36:30the samples that are that
36:31are garnered from that. And
36:33the other thing too is,
36:34you know, there's nothing worse,
36:35you know, particularly being the
36:36surgeon,
36:37then you do a a
36:39big operation.
36:40You think you help someone,
36:42and man, the melanoma
36:44is back. Right? And you
36:45say, did we miss an
36:46opportunity to maybe treat that
36:48person earlier with something that
36:49would be more effective?
36:53So again, this is just
36:54a little cartoon illustration of
36:56kind of a little bit
36:57more of that that concept
36:59of having these different t
37:01cells in the area. You
37:02know, if we take that
37:03out first,
37:04there's less for the immune
37:06system to recognize. So people
37:07were really saying, you know,
37:10what order should we do
37:11this at?
37:13So,
37:14again, one of the first
37:15thing was kind of the
37:16double therapy that that Brandy
37:18had talked to a little
37:19bit. And this was some
37:20of the early studies trying
37:21to say, okay, how do
37:22we get the right combination?
37:24One that we don't want
37:25to be too toxic,
37:27but one that we want
37:28to work. Right? Because we
37:29always balance. What is the
37:30treatment due to the tumor
37:32and what does it do
37:33to our patient? Right?
37:34Both are important.
37:38So this was kind of
37:39the the winner that then
37:40went through to the next
37:41round of trials.
37:44And we also said too,
37:45again, could we just do
37:46a single? Right. So this
37:48is what this was what
37:49we call the swab trial.
37:50That was the organization that
37:51did that did this across
37:53patients. This is just with
37:54a single type of immune
37:55therapy.
37:56Seeing a difference between in
37:58blue, the people who got
37:59immune therapy before surgery, the
38:01red are people who had
38:03surgery and then had the
38:04immune therapy,
38:05and seeing some responses.
38:08We think probably the doublet,
38:10you know, maybe a little
38:11bit stronger,
38:12but it's also got more
38:14side effects. But again, this
38:15is a big trial that
38:16was done called the Nadina
38:18trial. And it also said,
38:20why don't we learn
38:21from what the tumor does?
38:23Do we need to do
38:25you know, what kind of
38:26an operation do we need
38:27to do? Do we need
38:28to give people more treatment
38:30after? Right? So, you know,
38:32in in in our best
38:33circumstances, you know, if we
38:34give someone a therapy
38:36and
38:37the pathologist
38:38examines it and says all
38:39the melanoma's dead and been
38:40replaced,
38:41do they need to get
38:42more treatment? Right? So these
38:43are all of the things
38:44because, again, the treatments can
38:46have side effects. We don't
38:47know when they'll come. Some
38:48people will never get them.
38:49Sometimes they'll get them late.
38:51Right? So everything we say,
38:52okay. How can we be
38:53smarter about what we're doing?
38:56So again, in this again
38:57again in blue, the people
38:58who got the doublet
39:00immune therapy first. Right? That's
39:02the blue line. The red
39:04line under there. And when
39:05we look at, you know,
39:07did something happen?
39:08Was there an event that
39:09a tumor come back or
39:11not? You know, you see,
39:12you know, lasting, you know,
39:14almost to about three years,
39:16you know, there were people
39:17who had really, really good
39:18responses.
39:19And the thing that becomes
39:20actually the most important is
39:22when we break it down
39:23by
39:24in people who
39:25when the pathologist examined it
39:27and they had what we
39:28called a major pathologic response.
39:30Right? They examined. They said,
39:31man, this immune therapy took
39:33care of the tumor.
39:35The number of people that
39:36the melanoma then came back
39:37later
39:38was actually a rarer event.
39:40And again, this is kind
39:41of what we we talk
39:42about, you know, evolving, cutting
39:45edge. You know, it's taken
39:46many years to get there
39:48since the first trials.
39:50And we, again, we do
39:51worry. Right? We do worry
39:53if someone gets a a
39:54side effect as well. And,
39:56you know, even though we're
39:57we're intending to shrink the
39:59tumor and maybe having a
40:00good response,
40:01but, again, not everyone
40:03is gonna have a great
40:04response.
40:06And we're finding that out
40:07earlier too, so we can
40:08start thinking about what's the
40:10next thing. Okay. And that
40:11also becomes important and valuable.
40:16So just to to conclude,
40:18you know, there's other
40:19types of recipes that are
40:21being investigated.
40:22Right. So there's another type
40:24that some people here may
40:25have been exposed to something
40:27called lag three. There's a
40:28couple of different companies with
40:30different versions
40:31that's ongoing to see is
40:33that a better balance between
40:34getting a good response and
40:36less side effect.
40:38There's gonna be a big
40:39study that changed even how
40:41we manage people's lymph nodes.
40:43And now in the setting
40:44of people who have lymph
40:45nodes that we can feel,
40:46they get therapy.
40:48As a surgeon, do I
40:49have to take them all
40:49out?
40:50Am I are you gonna
40:51live longer and live better
40:53if I do that?
40:54Or
40:55maybe if you started with
40:56one or two, do I
40:57just take the ones that
40:58we know and we leave
40:59the rest of the lymph
40:59nodes? Almost what I do
41:01when I do a central
41:02node biopsy on folks.
41:04There's other blood markers again
41:05that people may be hearing
41:07a little bit about. I
41:08don't know if doctor Tran
41:09or doctor Ishizuko mentioned that
41:11things like circulating tumor DNA,
41:13complementary
41:14blood tests that may help
41:15us detect things and to
41:17say, well, if we see
41:18this combination,
41:19maybe we should continue to
41:21give people treatment, things that
41:22we learn, things that we
41:24adapt to by the knowledge
41:25that we garner.
41:26Probably the most important thing
41:28is the people who are
41:29not responding.
41:30What should we do for
41:31them? Right. So that's why
41:33when we're all done working
41:34in clinic, all of us
41:35go to the lab and
41:36we say, what what's the
41:38next thing that we can
41:39do and why we at
41:40our meetings that everyone's working
41:41hard to think about? What
41:42do we do for the
41:43people we can't help right
41:44now?
41:45Should we do it in
41:46people who have bad melanomas
41:48that don't go to lymph
41:50nodes that start in the
41:51skin that are just big
41:52and aggressive and we're worried
41:54about them?
41:55That's some of the things
41:56that are being studied.
41:57And again, with everything we
41:59wanna figure out as the
42:00earliest point
42:02whether things are responding.
42:04Right? Because those are the
42:05people we wanna continue. And
42:06again, if we can figure
42:07that out, we wanna stop
42:09a therapy that's not helping.
42:10Right? Because then we're only
42:11causing potential harm and not
42:14good.
42:15So
42:17with that, I will leave
42:18you with my favorite cartoon.
42:28Alright.
42:29As usual, I speak fast.
42:31So doctor Tran
42:38Kinda wish I had cartoons
42:40and
42:41pet videos now that again
42:43so I'm gonna kinda dovetail
42:45along to what doctor Alino
42:47had already started. We're gonna
42:48be talking about systemic therapies
42:50and how we think about
42:51treating advanced melanomas.
42:53I think one of the
42:54main takeaways that I want
42:56to familiarize everyone with tonight
42:58is a lot of these
42:59drugs that you may have
43:00heard about on the news
43:02or in clinic from your
43:03doctors, kinda recognizing
43:05exactly how they work, what
43:07kind of class of drugs
43:09they are, when we determine
43:11using one versus another because
43:13there are differences when one
43:14is actually more potent,
43:16more effective, less toxic versus
43:18another. And then how we
43:20also think about sequencing therapies
43:22too to carry on what
43:23doctor Lina had spoken about.
43:25And so melanoma, you know,
43:27we stage melanomas to try
43:28to figure out what we
43:29need to do after the
43:30fact. Right? How do we
43:31keep it at bay? How
43:32do we prevent it from
43:33coming back?
43:34So for stage one melanomas,
43:36you know, the overall survival
43:38is pretty good.
43:40Ninety nine percent of five
43:42years, ninety eight percent of
43:43people are alive without having,
43:45succumb to their melanoma
43:47for early stage one a's.
43:49And you can see oftentimes
43:51as the stage increases, meaning
43:54stage two melanomas being thicker,
43:55stage three melanomas
43:57involving those lymph nodes, stage
43:59four melanomas become metastatic
44:01that unfortunately
44:02those survival outcomes do drop
44:05off.
44:06So how can we intervene?
44:09So again, upfront early stage
44:11melanomas, they go directly to
44:12my surgical colleagues, doctor Alina,
44:14doctor Westlake.
44:15They just get cut out,
44:17you know, hopefully,
44:19you know, we can figure
44:20out, we can get get
44:21control over that. There are
44:23specific nomograms that are actually
44:24publicly available. We just plug
44:26in the thickness,
44:28some risk factors associated with
44:30the pathology and figure out
44:31exactly what the risk is
44:33for that limp that melanoma
44:34to travel into the lymph
44:36node to then just make
44:37a very personalized decision
44:39about whether or not a
44:40lymph node biopsy is needed.
44:42Because we wanna we don't
44:43necessarily want to recommend more
44:45surgery. That's not gonna change
44:47the clinical outcome.
44:49Thicker melanomas,
44:50again, those get excisions
44:52plus or minus the sentinel
44:53lymph node biopsy.
44:55And then right now we're
44:56trying to figure out, okay,
44:58after that stage two melanoma
45:00comes out, do we offer
45:01additional treatments
45:03due to help minimize the
45:04risk of recurrence?
45:06For stage three melanoma, certainly,
45:08that was the the paradigm.
45:11Now as we're learning more
45:12about how to treat these
45:14upfront,
45:15maybe a little bit of
45:16systemic therapy followed by surgery
45:19to help minimize the long
45:20term need for any additional
45:21therapy would actually be beneficial.
45:23And then we'll also talk
45:25about stage four disease or
45:26basically distant metastatic
45:28disease. So, basically, the melanoma
45:30has now traveled to other
45:31sites in the body.
45:34So when we think about
45:35melanoma specific survival,
45:37again, we're thankfully
45:39not focused on those individuals
45:41who saw doctor Leventhal had
45:43their early stage melanoma that
45:45was very thick or sorry,
45:47very thin excised.
45:48We're kind of focusing on
45:50where we can move the
45:52field, where we can make
45:53changes to help improve patient
45:56outcomes
45:56long term.
45:58And so,
45:59yeah, past studies have shown
46:01sometimes earlier interventions, not waiting
46:04necessarily until the diseases come
46:05back, but actually prophylactically
46:08just starting some form of
46:09treatment
46:10for these higher risk melanomas
46:12may actually be beneficial in
46:14decreasing the risk for recurrence.
46:16And so it's always,
46:19counterbalanced
46:19by toxicity
46:21too. Everything that we prescribe
46:22has certain side effects.
46:24And so does that make
46:25sense to the individual in
46:27front of us? Do those
46:28side effects
46:29outweigh the potential benefits,
46:32verse,
46:33vice versa.
46:35And I'm sorry again, they're
46:36like Doctor. Levinthal, there's a
46:38little bit of a disconnect,
46:39when the slides were compiled
46:41here.
46:42When we, we also then
46:44do consider new adjuvant treatment
46:46because these drugs can work
46:47very well in the metastatic
46:49setting. We're trying to see
46:51if they can work even
46:52better in the stage three
46:54setting
46:55or even moving them up
46:56front, giving a little bit
46:57of treatment followed by
46:59surgery. And then deciding based
47:01on the pathology, whether or
47:03not additional treatment is needed.
47:05Now we always hark about
47:07tumor profiling and these more
47:09advanced melanomas. You know, we
47:11gotta wait for the tumor
47:12profiling to come back before
47:14we can make a treatment
47:15recommendation.
47:16That's because about in half
47:18of skin related UV exposed
47:20melanomas,
47:22people can have a BRAF
47:23mutation
47:24and that can be a
47:25game changer when we talk
47:26about adjuvant treatment or treatment
47:28after surgery to help minimize
47:29the risk of recurrence.
47:32BRAF mutations are unfortunately exclusive
47:35to NRAS mutations. So you
47:36have one or the other
47:37upfront.
47:38You know, sometimes we have
47:40individuals who
47:42develop,
47:43nodal metal melanoma,
47:45and we don't really know
47:46where the primary site is.
47:48So sometimes these mutations
47:50also help us to decipher
47:51where that melanoma originated from.
47:54Sometimes melanomas can regress automatically,
47:57with a with an,
47:59immune response upfront.
48:02Acral melanomas tend to have
48:03kit mutations.
48:05Mucosal melanomas can oftentimes have
48:07kit mutations, and then uveal
48:09melanoma is its own separate
48:10thing. It generally has a
48:12distinct,
48:13mutational profile unique to that.
48:17The other thing aside from
48:19tumor mutational status, that BRAF
48:21mutation
48:23is tumor mutational burden too.
48:25So as you can imagine
48:27over that chronic lifetime of
48:28unfortunate sun exposure,
48:31mutations
48:32add up and so that
48:33what that translates to is,
48:35the increase in number of
48:36mutations per megabase of DNA.
48:39The higher you have basically
48:42the more mutations that you
48:43have that can increase your
48:45chances of actually responding to
48:48immune therapy, it's a catch
48:49twenty two.
48:51This actually led to the
48:52first tumor agnostic approval for
48:55an anti cancer treatment.
48:57So this led to the
48:58approval of immune therapy, regardless
49:01of the cancer type. If
49:02you had a high enough
49:03tumor mutational burden,
49:05melanomas
49:06given that sun exposure is,
49:07has one of the highest
49:09mutational burdens.
49:12So immunotherapy,
49:14you know, we, we hear
49:15a lot about different types
49:16of immune therapy, but there's
49:18actually a number of different
49:19flavors of immune therapy.
49:21There's what we consider those
49:23immune checkpoint inhibitors, those monoclonal
49:26antibodies that we give Ivy
49:27every few weeks.
49:29There's also cytokine therapies,
49:31which is kind of the
49:32old version of immune therapy
49:34that's now resurfacing and having
49:36a renewed life in terms
49:38of the emerging clinical trials.
49:40There is now approvals
49:42in adopted cell transfer
49:44to so t cell based
49:46therapies,
49:46till therapies.
49:48There's cancer vaccines that are
49:50in clinical trials
49:52there's also oncolytic virus
49:54all of these different mechanisms
49:57basically help to augment your
49:59own body's ability to fight
50:01off the cancer
50:03So there was a dearth
50:05of
50:05systemic therapy options thirty years
50:08ago. It was chemotherapy
50:10and stage four melanomas
50:12were inevitably
50:13fatal.
50:15Since then though, thankfully with
50:17the advent of immune therapy,
50:18immune checkpoint inhibitors, we've had
50:20this resurgence
50:22of in our research interest
50:24in how do we
50:26utilize the immune system,
50:28leverage it to our advantage,
50:29to attack and directly destroy
50:31melanoma cells. So thankfully in
50:33the past fifteen years, we've
50:35seen a lot of new
50:36developments,
50:37drug developments, small molecule inhibitors,
50:40that will help to combat
50:42melanoma.
50:43So,
50:45you know, ongoing research as
50:46evidenced by the ellipsis here.
50:48So more to come,
50:49recently there's optula, which is
50:51combination anti PD one anti
50:54lag three there's to benefit
50:55us that got approved for
50:57uveal melanomas.
50:59And then finally,
51:00lip Aliso, which is till
51:02therapy.
51:04So, as I said, there's
51:05different treatment buckets and a
51:06lot of people come to
51:08me and say, oh, my
51:09insurance labeled the immune therapy
51:11as chemotherapy. I'm confused. What
51:13am I getting exactly?
51:15So chemotherapy,
51:16we talk about it only
51:18in the setting where
51:20all else fails, just because
51:21we know
51:23a lot of these treatments,
51:24carbotaxel,
51:25carbazine,
51:27temozolomide
51:28temodar
51:29really have limited efficacy
51:31they're not really seen as
51:32curative
51:33and so they're also toxic
51:35so we kind of reserve
51:36them kind of as a
51:38last resort it's really not
51:40a viable option
51:41Then we have targeted therapies.
51:43So it's targeted
51:45specifically towards a mutation.
51:47So this is very personalized
51:49medicine here. So if you
51:51have these mutations then potentially
51:54there
51:54is a pill that can
51:56target that mutation.
51:57So the most common one
51:58that we see in melanoma
52:00are B RAF mutations. So
52:01we have B RAF and
52:03MEC inhibitors targeting that again,
52:05there are kit inhibitors that
52:06are NTRK inhibitors that are
52:08Ross inhibitors as well.
52:10Then there's what we traditionally
52:12think of as immune therapy.
52:14So drugs like ipinivo,
52:16up dual lag, which is
52:18nivo rella,
52:19and then the single agent
52:20anti PD ones, nivo or
52:22Keytruda pembrolizumab,
52:24and then kind of our
52:25old standard,
52:26cytokine therapy. So like high
52:28dose IL two, for example.
52:30And then finally,
52:31The next advent is cell
52:33therapy. So this is till
52:34this is tumor infiltrating leukocyte
52:37therapy. It's where we actually
52:39harvest,
52:40tumor, grow out the t
52:41cells,
52:42and reinfuse them into patients.
52:45It's a one time treatment,
52:46but it is quite,
52:48an involved,
52:49process.
52:51So immune therapy back in
52:52the day when I was,
52:54a medical student, we were
52:56giving high dose IL two.
52:57That was kind of the
52:59standard treatment
53:00for metastatic melanoma.
53:03As you can see, the
53:04overall survival
53:06probability for these patients, it
53:08wasn't great. It was also
53:09really toxic, very difficult for
53:11patients to get through lots
53:13lots of issues with blood
53:14pressure support,
53:17edema, etcetera.
53:18So since then, kind of
53:20the central,
53:22study looking at immune therapy
53:25evaluated a combination of ipi
53:27and evo. And there's a
53:28central idea that the more
53:29different types of immune therapies
53:31you combine,
53:32the higher the response rate.
53:34The trade off is the
53:35higher the toxicity too.
53:36And so for every individual,
53:38we make a very personalized
53:40judgment call about what their
53:42ultimate goals are and tailor
53:44the treatment based on how
53:45much disease they have, where
53:47that diseases
53:48have, so that we can
53:49hopefully reap the benefits of
53:50potential response without too much
53:52added toxicity.
53:54And so again, this is
53:56where the field has moved
53:57in,
53:58and it's generated a revolution
53:59not only in melanoma treatment,
54:01but also has trickled down
54:02to other cancer types as
54:04well.
54:05So this is just a
54:06simple,
54:07table of the various systemic
54:09treatment options,
54:11you know, on the left
54:12there,
54:12immune therapy,
54:14as well as the response
54:15rates and their mechanisms
54:17of action,
54:18on the right targeted therapy.
54:20So these are your BRAF
54:21and MEC inhibitors,
54:23and you can say, Oh,
54:24wait a minute.
54:25The objective response rate, the
54:27chances of responding to these
54:29small molecule inhibitors is actually
54:31higher than immune therapy.
54:33Why are we recommending immune
54:34therapy as the upfront treatment
54:36for, metastatic melanoma?
54:38The issue is actually
54:40you get a much more
54:42durable response, meaning the chances
54:44of actual cure
54:46are much higher if we
54:48go with immune therapy
54:50the response rates are high
54:51yes there are potential
54:53permanent side effects
54:55like endocrine
54:56issues
54:57but
54:58the response
54:59can be long lasting.
55:00We can potentially actually cure
55:02people and put them into
55:04long term remission with immune
55:05therapy
55:06as opposed to targeted therapy.
55:09So that's why we favor
55:10immune therapy upfront, and this
55:12has been actually evaluated
55:13in a dream seek trial.
55:16And then also as a
55:17second line option
55:19t cell therapy lifolucil as
55:21well is available.
55:23Lifolucil,
55:25made the headlines just because
55:26it was the first
55:28t cell based therapy
55:30that was approved for a
55:31solid tumor
55:32and again it's not a
55:33walk in the park
55:35which is why we don't
55:36start with till therapy up
55:38front
55:39again there's a chance that
55:40we could potentially cure people
55:41with immune check point inhibitors,
55:43those in, systemic immune therapies.
55:45So we really reserve till
55:47therapy for those people who
55:48are refractory to prior treatments.
55:51So till therapy is quite
55:53involved.
55:55Patients have to undergo rigorous
55:56evaluation
55:57for cardiac function, pulmonary function.
56:00They have to have relatively
56:02slow growing tumor. They're not
56:04gonna blossom out of control
56:06within the next, two months
56:08because one, you have to
56:09get them to surgery. Doctor
56:11Alino has to remove those
56:13those tumors. We have to
56:14send it to the company.
56:15The company has to dissect
56:17the tumor out, make a
56:19single cell suspension, grow those
56:21t cells out, hit them
56:22with cytokines,
56:24basically make billions of copies
56:25of those T cells.
56:27Once those cells are ready,
56:28we have to get the
56:29patient back in, give them
56:30some low doses of chemotherapy
56:33to basically suppress
56:38t cells to come back
56:38in.
56:40Those t cells then get
56:41reinfused
56:42while the patient's in the
56:43hospital, and then they subsequently
56:45get low doses of IL
56:46two to help
56:48cells to survive now that
56:50they're back in you.
56:51So it's a quite a
56:53process. Patients have issues with
56:55low blood cell counts for
56:57the first month. They oftentimes
56:59need transfusion
57:00support.
57:01It is a very expensive
57:04treatment.
57:05It's a very costly in
57:07terms of time treatment, time
57:08commitment too.
57:10And so after that, then
57:12the patient gets discharged. They
57:13recover.
57:14And then it's kind of
57:15a waiting game to see
57:16if those T cells respond.
57:19Now immune checkpoint inhibitors. Whenever
57:22we counsel patients on, on
57:24potentially considering this treatment,
57:26again, it's not without side
57:28effects. So there are a
57:29lot of autoimmune
57:30related side effects that could
57:32incur,
57:33as as a result of
57:35immune checkpoint inhibitors. And, basically,
57:37it's bottom line is inflammation.
57:39It can happen anywhere. It
57:41can happen anytime
57:43so where that occurs
57:45kind of translates to the
57:46side effects so most common
57:47things are fatigue rash
57:50depending on the regimen
57:51sometimes diarrhea
57:53joint arthritis
57:55it can result in some,
57:57permanent side effects like type
57:59one diabetes,
58:01permanent loss of your thyroid
58:03function, pituitary
58:04adrenal function.
58:07Some things are we can
58:08replace with,
58:10medications like thyroid medications,
58:13low doses of steroids.
58:14Some a lot of these,
58:16side effects,
58:18are treatable, though. There are
58:20some very high risk side
58:21effects that we oftentimes have
58:23to counsel patients about
58:25because it can lead to
58:26lung inflammation, heart inflammation,
58:28inflammation of the nerves called
58:30myasthenia,
58:31gravis. And so,
58:33it is not without its
58:35risks.
58:36Now,
58:37you know, back in the
58:38day when these drugs were
58:39under clinical trial development, we
58:40were afraid to give it
58:42to people who had existing
58:43autoimmune issues.
58:45Thankfully, what we've discovered
58:47through the course of having
58:48these drugs available and trying
58:50to push the field to
58:51make them available for for
58:53more people is that a
58:55lot of these side effects,
58:56they don't necessarily
58:58flare in people who have
58:59autoimmune disease.
59:01Some things like PMR will,
59:03but other things like lupus,
59:05we can actually give these
59:07patients,
59:08with existing lupus, these immune
59:10checkpoint inhibitors.
59:11And oftentimes, we can we
59:13can get by, and they
59:14have a fantastic response.
59:16And so again it's not
59:18an absolute no that if
59:20you have an autoimmune disease
59:22that these therapies will not
59:24work for you or not
59:25safe for you.
59:26And so again this is
59:27where a clinical
59:29judgment
59:30kind of weighing the risk
59:31and benefits come into hand.
59:33So kind of just the
59:34lay of the land in
59:35terms of how we think
59:37about metastatic,
59:39melanoma treatment. So kind of
59:41up top on the far
59:42right here, you know, I
59:43kinda listed the drugs,
59:45in terms of efficacy.
59:47Again, the more efficacious, the
59:49potentially
59:50the higher the side effects.
59:51So we have ipinivo,
59:53that's kind of our tried
59:54and true regimen. If you
59:55have lots of disease,
59:57critical sites of disease, like
59:59brain metastases,
01:00:00That's one that we will
01:00:01oftentimes try upfront
01:00:03if we can think you
01:00:05can tolerate the side effects.
01:00:07Because, again, we don't wanna
01:00:08harm people,
01:00:10have a detriment to their
01:00:11quality of life with these
01:00:12treatments.
01:00:13Next is Zopdulilag.
01:00:15So people who have low
01:00:16volume disease will oftentimes try
01:00:18this first. And again, if
01:00:20there are side effects, we
01:00:21can deescalate
01:00:23to single agent Nivo or
01:00:25pembro.
01:00:26And if they don't have
01:00:27the response that we like,
01:00:28we can always escalate to
01:00:30ipinivo too.
01:00:31There's targeted therapies.
01:00:33And, again, there those come
01:00:35also in different flavors,
01:00:37and then cell therapy.
01:00:40So just a few,
01:00:41comments about some specific locations.
01:00:44So brain metastases.
01:00:46Doctor Kluger, you know, has
01:00:47a lot of clinical trials,
01:00:49a lot of investigation, and
01:00:50how do we improve responses
01:00:52for individuals with brain metastases.
01:00:55You know, melanoma,
01:00:56for whatever reason,
01:00:58probably from the neuroactogen
01:01:00merle origin of these cells,
01:01:02has a tendency to go
01:01:04to the brain.
01:01:06These lesions are not benign,
01:01:07obviously. They can bleed. They
01:01:09can cause seizures, they can
01:01:11cause edema, brain swelling,
01:01:13neurologic,
01:01:15loss of function.
01:01:16And so we actually do
01:01:18have better treatments now, more
01:01:19effective therapies that actually penetrate
01:01:22into the brain. We have
01:01:23radiation therapy that we can
01:01:25combine
01:01:26with these systemic therapies,
01:01:29but we still need ongoing
01:01:31research in radiation necrosis.
01:01:33That's where there's a lot
01:01:35of,
01:01:35cyclical inflammation in the brain
01:01:37that can lead to swelling
01:01:38too.
01:01:40You know, oftentimes,
01:01:41individuals ask me, okay.
01:01:44How do I know the
01:01:44treatment's working?
01:01:46We have to wait,
01:01:48you know, usually at least
01:01:50six weeks, if not three
01:01:51months, in order to figure
01:01:52this out.
01:01:53Because the issue is if
01:01:54we scan too soon,
01:01:56there is a phenomenon called
01:01:58pseudo progression.
01:01:59Those immune cells are activated
01:02:01from these systemic therapies.
01:02:02They can infiltrate into the
01:02:04tumor,
01:02:05cause a little bit of
01:02:06swelling, if you will, in
01:02:07that tumor whereby that tumor
01:02:09looks bigger on the scans,
01:02:10but it's actually because those
01:02:12immune cells are trying to
01:02:13get in there to do
01:02:14their job. And if you
01:02:15just wait a little bit
01:02:16longer, have a little patience,
01:02:18hopefully a little faith, and
01:02:20a few more prayers,
01:02:21then
01:02:22subsequently we see tumor shrinkage.
01:02:24And so that's why, unfortunately,
01:02:26we can't scan too soon.
01:02:27We have to,
01:02:29put our faith in these
01:02:30medications sometimes early on. And
01:02:32particularly if you're doing well,
01:02:34and symptoms are not any
01:02:35worse,
01:02:36oftentimes that's a sign of
01:02:38pseudo progression rather than true
01:02:40progression.
01:02:42Alright. So adjuvant treatment paradigms.
01:02:46So we talked about moving
01:02:48a lot of these effective,
01:02:50medications
01:02:51in the stage four setting
01:02:52early on to see if
01:02:53we can reduce recurrence risk.
01:02:56And so in stage three,
01:02:58you know, anti PD one
01:02:59drugs, so these are things
01:03:00like nivolumab,
01:03:02pembrolizumab,
01:03:03they do recur reduce recurrence
01:03:06risk by about fifty percent.
01:03:08However, they don't really improve
01:03:10survival.
01:03:11So what's our endgame? What's
01:03:12our target here? We need
01:03:14patients to live longer. We
01:03:15need them to do well
01:03:17longer.
01:03:18And so sometimes for for
01:03:20individuals, again, and this is
01:03:21where personal
01:03:22decision kind of priorities come
01:03:24into play. Maybe those side
01:03:26effects
01:03:26don't bode well if you're
01:03:28already kinda struggling and have
01:03:30other health issues.
01:03:31And so in those particular
01:03:33settings, if you do not
01:03:34have a BRAF mutation,
01:03:35sometimes a watch and wait
01:03:37approach,
01:03:38is actually makes more sense.
01:03:41If you do have a
01:03:41BRAF mutation,
01:03:43they these medications for stage
01:03:45three patients actually reduce recurrence
01:03:47risk by half, but they
01:03:48have also are starting to
01:03:50show improvements in survival too.
01:03:52So that's where waiting for
01:03:54that tumor mutational status to
01:03:56come back from the tumor
01:03:57resection
01:03:58actually does really impact how
01:04:00we think about treating individuals
01:04:02too. For stage two patients,
01:04:05anti PD one has been
01:04:06FDA approved, so nivolumab,
01:04:09pembrolizumab.
01:04:10However,
01:04:11the response, the benefit is
01:04:13a little bit less than
01:04:14stage three patients, and, again,
01:04:15there's no overall survival benefit.
01:04:20Alright. So neoadjuvant,
01:04:22I think doctor Alino has
01:04:23covered that very well, so
01:04:25we'll kinda skip over this.
01:04:28But really kind of, just
01:04:30and, again, just to kinda
01:04:31we we like to go
01:04:32over a case case reports.
01:04:35Okay?
01:04:36We're we're gonna pretend you
01:04:37guys are all medical trainees
01:04:39now that you've been you've
01:04:40lived the experience.
01:04:43So for example, let's think
01:04:44about, you know, a patient
01:04:45who had a right,
01:04:47abdomen melanoma.
01:04:49Stage three b,
01:04:51it was ulcer
01:04:53nonulcerated,
01:04:54but it had microsatellite.
01:04:55So there are little,
01:04:57areas of tumor
01:04:58adjacent to the primary site.
01:05:02BRAF,
01:05:03mutation status was positive, meaning
01:05:05the patient had a BRAF
01:05:06mutation.
01:05:08There was a clinically palpable
01:05:10lymph node, and so the
01:05:11decision was, as one of
01:05:13doctor Alina's paradigms,
01:05:15to treat with anti PD
01:05:16one therapy upfront.
01:05:18We gave two doses and
01:05:20actually the patient developed myocarditis,
01:05:22which is one of the
01:05:23most concerning side effects.
01:05:25And again, this kind of
01:05:26highlights that sometimes high risk
01:05:28sometimes comes with high reward
01:05:30too because what happened is
01:05:32that the tumor shrank.
01:05:35We did take a while
01:05:36for us to treat the
01:05:38myocarditis,
01:05:39get it under control to
01:05:40get the patient safely to
01:05:41surgery.
01:05:43However,
01:05:44so when that lymph node
01:05:45came out, there was still
01:05:46some viable melanoma. A lot
01:05:48of it was necrotic.
01:05:50The patient, because of that
01:05:52BRAF status, ended up getting
01:05:53an additional year of BRAF
01:05:54MEK inhibitors and remains disease
01:05:57free to this day. Myocarditis
01:05:59treated
01:06:00doing well.
01:06:02And so again, kind of
01:06:03leading into
01:06:04my colleague, Doctor. Ishizuka, who's
01:06:06gonna talk to you about
01:06:07about where the field is
01:06:08moving.
01:06:10We're gonna talk about where
01:06:12we can,
01:06:13move in terms of
01:06:15cancer vaccines,
01:06:16cytokine therapies,
01:06:18and adoptive cell therapies to
01:06:20try to push this forward.
01:06:22Thank you.
01:06:38Great. Well, thank you so
01:06:40much for the opportunity to
01:06:41be here today and to
01:06:42tell you a little bit
01:06:43about clinical trials here at
01:06:45Yale and Melanoma.
01:06:47So a couple of things
01:06:48I want to impart in
01:06:50the course of of our
01:06:51conversation tonight.
01:06:52One is just to know
01:06:54that that trials are are
01:06:56strong treatment options
01:06:57that going into the selection
01:06:59for a trial to be
01:07:00even considered at Yale, we
01:07:02meet together as a group.
01:07:04We discuss the merits. We
01:07:05make sure that there's a
01:07:06that we see a benefit
01:07:08for our patients to even
01:07:09put it on the roster
01:07:10of things we consider.
01:07:13That leads into number two,
01:07:15which is that
01:07:17whenever we suggest a clinical
01:07:19trial as a consideration,
01:07:20it's because we think that
01:07:22it is potentially,
01:07:24a thing that could offer
01:07:25offer benefit and the most
01:07:26benefit
01:07:27to our patients.
01:07:29The third thing is that
01:07:30our clinical trial portfolio
01:07:32is always evolving,
01:07:34that
01:07:35you know, I'll talk about
01:07:36some of the trials that
01:07:37are available tonight, but at
01:07:39any given day, I won't
01:07:40try and cover every single
01:07:41trial. And at any given
01:07:43day, that trial portfolio
01:07:45may continue to evolve. So
01:07:47it's always worth a conversation
01:07:48with us at any stage
01:07:50of care. Sometimes we have
01:07:51trials for earlier stage disease,
01:07:53sometimes for later stage disease.
01:07:55So it's always worth that
01:07:56conversation.
01:07:59Many of you will know
01:08:00this. Some of you will
01:08:01have participated in clinical trials,
01:08:02but clinical trials are are
01:08:04carefully designed studies. They're carefully
01:08:06designed treatments that start with
01:08:08a strong scientific rationale,
01:08:10usually
01:08:11years of of studies and
01:08:13and all sorts of experimental
01:08:14models,
01:08:16as well as kind of
01:08:17safety testing and and,
01:08:19you know, prior to ever
01:08:20becoming a clinical trial.
01:08:22There's a whole infrastructure of
01:08:24oversight for safety here at
01:08:26Yale and for the clinical
01:08:27trials that are run nationally.
01:08:31And that in many cases,
01:08:32clinical trials mean more frequent
01:08:34points of contact, right, for
01:08:36safety monitoring and so that
01:08:37we can observe,
01:08:38what's happening with the trial,
01:08:40in in you.
01:08:43Our fundamental motivation
01:08:45is twofold. Right?
01:08:47One thing is that we
01:08:48want to move the field
01:08:49forward.
01:08:50This is a group of
01:08:51people that go to bed
01:08:52thinking about these things. They
01:08:53get up thinking about these
01:08:54things.
01:08:55Every patient that we can't
01:08:57help stays with us. And
01:08:59so more than anything, we
01:09:00wanna put ourselves out of
01:09:01business. We wanna create new
01:09:02treatment options.
01:09:04And so there is a
01:09:05strong motivation to move the
01:09:06field forward scientifically.
01:09:08But the other thing we're
01:09:09looking for is to give
01:09:10the best options and give
01:09:11a greater array of options
01:09:12today.
01:09:14And so, you know, when
01:09:16we're thinking about trials, we're
01:09:17also doing that. We're thinking
01:09:18about how do we create
01:09:19a portfolio of options at
01:09:20as many stages of care
01:09:22as we can,
01:09:23and how do we pick
01:09:24the things and and look
01:09:26for the best opportunities
01:09:27that we think have, the
01:09:29greatest chance of benefit.
01:09:32So this is the guiding
01:09:34principle. What is best for
01:09:35the patient in front of
01:09:36me? Anytime we're having a
01:09:38trial conversation,
01:09:39that's what that's what we're
01:09:40thinking about. If we think
01:09:42that standard therapies are the
01:09:43best option for you, we
01:09:45will tell you in a
01:09:46very straightforward way.
01:09:49A question that sometimes comes
01:09:51up, people say, and I've
01:09:52heard my patients say to
01:09:53me, I don't wanna be
01:09:54a guinea pig. I don't
01:09:55wanna be I don't wanna
01:09:56be experimented on.
01:09:58And I think there's a
01:09:59couple things to think through
01:10:00in response to that question.
01:10:01Right? Some of them I've
01:10:03already kind of laid out
01:10:05that this trial never made
01:10:06it here unless we had
01:10:07thought it had a chance
01:10:08of benefit. And then fundamentally,
01:10:11we wouldn't be suggesting it
01:10:13if we didn't think it
01:10:14was as good or better
01:10:16than the standard of care
01:10:17options that we can offer
01:10:19at that time.
01:10:20And so, you know, there's
01:10:22a lot that goes into
01:10:23the process depending on the
01:10:24phase of the trial, but
01:10:25there's always a tremendous amount
01:10:27of of oversight,
01:10:29both within the clinic here
01:10:30and actually a whole staff
01:10:31of people outside of the
01:10:33clinic,
01:10:33many of which you get
01:10:34to know if you participate
01:10:36in, well, they'll come into
01:10:37the clinic as well in
01:10:38a clinical trial.
01:10:40So
01:10:41I wanna think through a
01:10:43couple of the the types
01:10:45of trials
01:10:46that are
01:10:47going on here at Yale
01:10:48now. I won't spend a
01:10:50long time on them. You
01:10:51could spend an hour talking
01:10:53about each of them, and
01:10:53I I think you guys
01:10:54wouldn't like that that much.
01:10:55But,
01:10:57you know, I'll talk about
01:10:58a couple of different lanes
01:10:59of of therapy.
01:11:00Right? A frontline study for,
01:11:03you know, if you haven't
01:11:04started treatment and actually some
01:11:06studies that are available
01:11:08even if if you've gone
01:11:09through and progressed through a
01:11:11prior treatment. Right? In some
01:11:13cases, while studies even earlier
01:11:14phase than these as well.
01:11:17And, you know, as a
01:11:18as a kind of framework
01:11:20for how we're thinking about
01:11:21this, doctor Tran laid out,
01:11:23as well as the targeted
01:11:24therapies, the great benefits that
01:11:26have come with the development
01:11:27of the immunotherapies.
01:11:28And so a lot of
01:11:29the things you'll hear me
01:11:30talk about, the ideas that
01:11:31are being tested in the
01:11:32clinic, focus on the, this,
01:11:34this general concept of how
01:11:36do we make the immune
01:11:37system work better against cancers.
01:11:39Right? You'll hear a lot
01:11:40of that.
01:11:41Okay.
01:11:42So
01:11:44just briefly,
01:11:45this is, the the first
01:11:47trial is one for patients
01:11:48who have not yet started
01:11:50therapy. It is a a
01:11:51frontline trial.
01:11:53It uses
01:11:54two agents, p d one
01:11:56and and LAG three that,
01:11:58doctor Tran described.
01:11:59In this case, it's testing
01:12:01a different type of PD
01:12:02one and LAG three, different
01:12:03types of drugs that target,
01:12:05at target these checkpoints
01:12:07and at different doses. And
01:12:09and, you know, part of,
01:12:10I guess, the learning there
01:12:11is it's it's potentially,
01:12:14we we do see, although
01:12:15many of these drugs target
01:12:17the same fundamental immune targets,
01:12:20that they can work in
01:12:20slightly different ways, that the
01:12:22the way you make the
01:12:23molecules, the way that you
01:12:25dose the molecules
01:12:26can have an effect on
01:12:27the overall immune response. And
01:12:29so, you know, the hypothesis
01:12:31here is that even though
01:12:32these two arms are targeting
01:12:34the same two sets of
01:12:35immune checkpoints,
01:12:37that,
01:12:37by using a different drug
01:12:39that is tuned differently and
01:12:40at different doses, that you
01:12:41may be able to get
01:12:42a better response.
01:12:45The the other trials I'll
01:12:47talk about are for later
01:12:48lines of care, so patients
01:12:50who have have progressed through
01:12:51some prior therapy.
01:12:53And, this is this is
01:12:54an oral medication
01:12:56called a PTPN
01:12:57two inhibitor. We won't quiz
01:12:59you on the the acronyms
01:13:00at the end.
01:13:02But the idea here is
01:13:03that you're doing a couple
01:13:04of separate things that are
01:13:06are different to improve the
01:13:07immune system. One is that
01:13:09you're helping,
01:13:10some of your immune active
01:13:12your active immune cells called
01:13:13t cells to function better.
01:13:15And the other is that
01:13:16you're targeting the tumors to
01:13:18become more responsive to some
01:13:20of the signals that are
01:13:21made by the t cells.
01:13:24Our our next trial that
01:13:26I'll mention
01:13:27is a way of doing
01:13:28two of the things that
01:13:29doctor Tran mentioned. She mentioned
01:13:31kind of cutting the brakes
01:13:32on the immune system with
01:13:33immune checkpoint inhibitors, but also
01:13:36kind of giving cytokines,
01:13:38that can sort of feed
01:13:40the the immune cells to
01:13:41help them grow and function.
01:13:43So in this trial, you're
01:13:44trying to combine those two
01:13:45ideas. And if you remember,
01:13:47doctor Tran mentioned that one
01:13:49of the problems with some
01:13:50of the cytokines is that
01:13:51they can have toxicities
01:13:53when given systemically, problems with
01:13:54blood pressure or other issues.
01:13:56And so in this case,
01:13:57you're trying to deliver
01:13:59this immune,
01:14:00cytokine just to the cells
01:14:02that need it. Right? And
01:14:03so that's that's one idea.
01:14:06Another variant of this idea
01:14:08that works along a similar
01:14:10line but using a different
01:14:11type of immune stimulatory
01:14:13signal is is this trial
01:14:14by Asher Bio using a,
01:14:17an agent that targets an
01:14:18immune cells called CD eight
01:14:20t cells and delivers to
01:14:22them this immune activating cytokine
01:14:24called IL twenty one.
01:14:26And so, you know, the
01:14:28idea here,
01:14:29it may work out to
01:14:30be that different patients will
01:14:31benefit from different things, and
01:14:33that's part of what we're
01:14:33trying to learn here as
01:14:34well.
01:14:37Finally,
01:14:39there's there's a trial that
01:14:40tries to take the to
01:14:42to try to tries to
01:14:43take out a negative,
01:14:46sponge that blocks an immune
01:14:48activating cytokine from working. So,
01:14:50again, this is an antibody
01:14:51therapy, but one that will
01:14:52actually,
01:14:53block the inhibitor.
01:14:55And a lot of the
01:14:56the fundamental science for for
01:14:57tumor immunology for this pathway
01:14:59was worked out here at
01:15:01Yale.
01:15:02But the hope is that
01:15:03this, this type of approach
01:15:06will take an important break
01:15:08off of the immune system
01:15:09and make it work better.
01:15:13You know, doctor Tran kind
01:15:15of weighed caught risks and
01:15:16benefits. You have to think
01:15:18about that with clinical trials
01:15:19as well.
01:15:21You know, in terms
01:15:22of cost, cost to to
01:15:24the patient,
01:15:25standard of care portions of
01:15:27the visit are generally covered
01:15:28by insurance, and then the
01:15:30study drug and study specific
01:15:31tests are usually paid for
01:15:33by the trial sponsor, but
01:15:35it doesn't mean that there
01:15:36cannot be any extra burden
01:15:38of travel and of time.
01:15:40In many cases, you're talking
01:15:42about further visits with us.
01:15:45And so that means, you
01:15:46know, getting you here to
01:15:47the clinic or at some
01:15:48in some cases, we can
01:15:50offer trials at our satellites
01:15:51sites as well. So it's
01:15:52not always here, but in
01:15:54many cases, the trials are
01:15:55centralized here.
01:15:57And then, of course, there's
01:15:58the time component.
01:16:00This added oversight for safety
01:16:02often means a a greater
01:16:04amount of time spent, you
01:16:05know, coming to clinic and
01:16:06and being with us in
01:16:07clinic.
01:16:10I just wanna leave you
01:16:11with, you know, the this
01:16:12idea again that,
01:16:15it's less about any particular
01:16:17trial that I I kind
01:16:18of talked very briefly about
01:16:19today and more about this
01:16:21overall framework,
01:16:22that,
01:16:23you know, these are are
01:16:25options that are reasonable to
01:16:26consider and that this is
01:16:27a conversation that we'd welcome
01:16:29having with with any of
01:16:31you or anyone,
01:16:32at any point.
01:16:34With that, I'll wrap up,
01:16:35and thank you.
01:16:43Have our our panels to
01:16:45come up to the front.
01:16:57But you guys have listened
01:16:58to us
01:16:59talk,
01:17:00And you haven't left yet,
01:17:01so that's always a good
01:17:02sign.
01:17:03But,
01:17:05you know, this is an
01:17:06opportunity we want all of
01:17:07you guys to
01:17:08ask us questions, anything that's
01:17:10come up during the talks,
01:17:12anything at all, and doctor
01:17:14Kluger will will moderate that.
01:17:16Excellent
01:17:17job. Yes. Let's do that,
01:17:19please. Let's start off with
01:17:20doctor Westwick, if you wouldn't
01:17:22mind. Thank you. Thank you.
01:17:25Yeah. I'm.
01:17:26I'm a plastic surgeon, and
01:17:28I work with the melanoma
01:17:29team together with doctor Alina.
01:17:32And Carlos, the PA who
01:17:33keeps me straight.
01:17:36Pretty much, you know, my
01:17:37job is
01:17:38to try to help
01:17:40any patient to get rid
01:17:41of their melanoma from a
01:17:42surgical standpoint.
01:17:44And being a plastic surgeon,
01:17:46when someone,
01:17:47including myself, makes a hole,
01:17:49I need to fix it.
01:17:50So that's my job.
01:17:54My name is Carla Becerra.
01:17:56I'm a surgical PA. I
01:17:57work with, doctor Westwick, doctor
01:17:59Lino, and doctor Khan sometimes
01:18:01as well.
01:18:03I've been a surgical PA
01:18:04here at Yale for almost
01:18:06nine years, and I've been
01:18:07in the melanoma field for
01:18:09thirteen.
01:18:11So I work with an
01:18:12incredible team, and I'm very
01:18:13happy to answer questions today.
01:18:16John Levinthal, we met earlier.
01:18:18Nice to see many familiar
01:18:19faces in the crowd.
01:18:22I'm Saj Khan. I'm one
01:18:23of the surgical oncologists. I'm
01:18:24fortunate to be doctor Aluno's
01:18:26partner,
01:18:27and I've been at Yale
01:18:28for about thirteen years now.
01:18:31Hi there. My name is
01:18:32David Schonfeld. I'm one of
01:18:33the medical oncologists here. So
01:18:35I I treat people with
01:18:36some of the the systemic
01:18:37therapies and clinical trials you
01:18:38just heard about, and I
01:18:39also see patients for follow-up
01:18:40and surveillance, and happy to
01:18:42take some questions.
01:18:45Thank you. So who's gonna
01:18:46brave it and ask a
01:18:47question?
01:18:48Anybody?
01:18:52Yes. Thank you. Doctor Tran's
01:18:54presentation, which was very interesting,
01:18:57and the the one slide
01:18:58in talking points around
01:19:01the current treatment paradigms,
01:19:05ipionivo,
01:19:05is that only a suggested
01:19:07course of action for stage
01:19:08four and not stage three
01:19:11patients now?
01:19:13Okay. I'm gonna let doctor
01:19:14I don't want to ask
01:19:14you. Take that one. So,
01:19:16so ipionivo is one of
01:19:18our standard
01:19:19go tos. You know, we
01:19:20we use it very commonly
01:19:21as Doctor. Tran mentioned for
01:19:23stage four patients.
01:19:24There's a couple flavors of
01:19:26giving it. We don't it's
01:19:28not the only option. There
01:19:29are other immunotherapies,
01:19:30especially another combo,
01:19:32that that
01:19:33comes with a little less
01:19:35efficacy, but a fewer side
01:19:37effects. So we we weigh
01:19:38always the, you know, the
01:19:39the patient's disease and and
01:19:40the specific,
01:19:41you know, medical history and
01:19:43other factors that go into
01:19:44it. But it is one
01:19:45of the more common one
01:19:45we use for stage four,
01:19:47and we are starting to
01:19:48use variations of it for
01:19:50earlier stage and and what
01:19:51doctor Tran and doctor Alino
01:19:53mentioned for what's called the
01:19:54neoadjuvant paradigm. So patients who
01:19:56need a little therapy before
01:19:58going to surgery, let's say
01:19:59because there's a palpable lymph
01:20:00node and we wanna give
01:20:01them something beforehand,
01:20:03doing a couple cycles of
01:20:05ipi nivo in a in
01:20:06a particular way way of
01:20:08dosing it is is one
01:20:09of the standard things we
01:20:10do now or or consider
01:20:11at least. But can I
01:20:13just add in there was
01:20:14a big trial where they
01:20:15compared they took state they
01:20:17took stage three melanomas out
01:20:19and then gave AP and
01:20:21Nivo, like, the two drugs
01:20:22versus the one drug, and,
01:20:23actually, there was a better
01:20:25outcome with one drug than
01:20:26with two?
01:20:27So it has been studied.
01:20:28It's just not beneficial.
01:20:31Good thing. So, I mean,
01:20:32I I'm a no longer
01:20:33surprised myself. So as a
01:20:34stage three patient,
01:20:36ipi and nivo is no
01:20:37longer a course of recommended
01:20:39action.
01:20:40Subjected. Stage three patients. That's
01:20:42been taken out. If it's
01:20:43already been taken out, yeah,
01:20:44we don't we don't generally
01:20:45use it there. But if
01:20:46it hasn't been taken out?
01:20:48Sometimes. Yeah. Yeah. It is
01:20:49a consideration. Yeah. If it's
01:20:51if if you're a stage
01:20:51three patient and there's some
01:20:53some disease we could feel,
01:20:56you know, it's something we
01:20:57would talk about and consider,
01:20:58yeah, for the right person.
01:20:59Yeah.
01:21:01Yes.
01:21:02Give us a brief definition
01:21:04of adjuvant and neoadjuvant.
01:21:07Okay. I'm gonna give that
01:21:09one to doctor Schonfeld again.
01:21:11Okay. I was gonna I
01:21:11was gonna hand it off
01:21:12to one of the surgeons.
01:21:13So so yeah. So,
01:21:15adjuvant,
01:21:16means after a more definitive
01:21:18thing, like a surgery typically.
01:21:20So adjuvant is after surgery,
01:21:22and then,
01:21:23neoadjuvant, and it can be
01:21:25any therapy. So adjuvant radiation,
01:21:26adjuvant systemic therapy, so an
01:21:28IV drug or a pill,
01:21:30And then neoadjuvant means before
01:21:31that more definitive therapy like
01:21:33a surgery. So that would
01:21:34be do that intervention like
01:21:36the, ipinivo, the immunotherapy
01:21:39first, and then go for
01:21:40the surgery. So it's either
01:21:42before or after the more
01:21:43definitive option, which is usually
01:21:45surgery.
01:21:46That's great feedback. Next time,
01:21:48we'll start with defining that.
01:21:50Okay. Thank you.
01:21:53Any other questions? I don't
01:21:55understand. What would be the
01:21:56surgery for a stage three
01:21:57patient
01:21:58with melanoma?
01:22:00Right.
01:22:01So so are you talking
01:22:02about specifically if they get
01:22:03what that that treatment beforehand
01:22:05and then they are you
01:22:06know, if you get the
01:22:07ipi nivo beforehand?
01:22:09If you're a stage three
01:22:10patient,
01:22:11what what would be a
01:22:12definition of a type of
01:22:13surgery that would be
01:22:15recommended?
01:22:16Maybe I'll hand that off
01:22:17to doctor Khan or doctor
01:22:18Westlake to
01:22:20And to be clear, sir,
01:22:21you're asking about lymph node
01:22:23positive disease.
01:22:24So,
01:22:25the surgery would generally be,
01:22:26you know, removing the primary
01:22:28tumor where it started from.
01:22:29So wide margin resection. So
01:22:30one centimeter for some tumors,
01:22:33two centimeters for additional tumors
01:22:34depending on the depth. And
01:22:36then, formal lymphadenectomy
01:22:37is what we'll often do,
01:22:39you know, particularly for axillary
01:22:41lymph node disease.
01:22:43You know, for,
01:22:44groin disease and pelvic diseases,
01:22:46things have changed and shifted
01:22:47a little bit, and there's
01:22:48less surgery that's being performed,
01:22:49but, an at lymphadenectomy.
01:22:52Which is sorry. Removing the
01:22:54lymph removing the lymph nodes
01:22:55from that basin. All of
01:22:56the lymph nodes.
01:22:58Yeah. We're probably becoming I'd
01:23:00love to see what doctor
01:23:00Alina says, but we're probably
01:23:02doing a little bit there
01:23:03was a time where we
01:23:04so there's different three levels
01:23:06of lymph nodes,
01:23:08level one, two, and three,
01:23:10and it's it's pretty aggressive.
01:23:12But,
01:23:13with immune therapy, we're probably
01:23:14not necessarily removing level three
01:23:16lymph nodes anymore. So,
01:23:18maybe let doctor Alino answer
01:23:19that. Yeah. So, you know,
01:23:22you can be in the
01:23:23same stage three bucket,
01:23:25and I can take out
01:23:26your melanoma.
01:23:28We do that sentinel node.
01:23:29We only find microscopic
01:23:30disease, and we learned that
01:23:32by taking out more lymph
01:23:33nodes, all we do is
01:23:35increase risk of swelling, and
01:23:36we actually don't make anybody
01:23:38live any longer. So in
01:23:40people who are still stage
01:23:41three, where you were diagnosed
01:23:43but it was microscopic, I
01:23:44told you I couldn't see
01:23:45it. The pathologist would have
01:23:46to tell us in a
01:23:47couple of days. You guys
01:23:48have heard my spiel. Okay?
01:23:50That's different than someone who
01:23:52comes into the clinic
01:23:54the first time that we
01:23:55meet
01:23:56them and we say,
01:23:58you have another spot, not
01:24:00just where the melanoma was.
01:24:01We feel something or something
01:24:03causes us to say, I'm
01:24:05really worried about your melanoma.
01:24:06Let's get a scan now.
01:24:08That's not microscopic
01:24:09disease anymore, and that's when
01:24:11we're talking about giving people
01:24:13some either an upfront therapy
01:24:15with a single or a
01:24:16double agent. Now that's very
01:24:18different than
01:24:19you come in.
01:24:21It's microscopic disease.
01:24:23We don't know if you'll
01:24:24be only
01:24:25the one in five person
01:24:27where you'll have more disease
01:24:28in the lymph nodes. That's
01:24:29why we don't take them
01:24:30all out. And that's when
01:24:32you meet with one of
01:24:33the colleagues, and they say,
01:24:34let's do the testing. You
01:24:36know? We don't have ev
01:24:37any evidence that there's any
01:24:38disease we can see on
01:24:39scans when we get the
01:24:40CAT scans or PET scans
01:24:42or the MRIs, and then
01:24:43we're we're trying to make
01:24:45that judgment.
01:24:46Do you need more? Are
01:24:47you gonna be the ones
01:24:48who are gonna be okay?
01:24:49And, again, that's one of
01:24:50the things that's really important
01:24:51that we all struggle with.
01:24:52Right? Because if we knew
01:24:53your melanoma was gonna come
01:24:54back, we'd have a different
01:24:56conversation.
01:24:56If we knew you're gonna
01:24:57have a toxicity,
01:24:59we'd have a different conversation.
01:25:00If we knew we could
01:25:01wait three years,
01:25:03then your melanoma would come
01:25:04back. You'd have three great
01:25:05years. You'd come and have
01:25:07to see us, but you
01:25:08know, and then it would
01:25:09come back, but you knew
01:25:10you had three good years
01:25:11where you didn't have to
01:25:12be exposed to any of
01:25:13the treatments. When every single
01:25:14one of you guys is
01:25:15coming in,
01:25:17and I encourage, you know,
01:25:18if if your doctors aren't
01:25:19speaking to you like that,
01:25:21that's when we're talking about.
01:25:22What are the pluses? What
01:25:23are the minuses?
01:25:25What are our theoretical risks?
01:25:27What are the fixed risks?
01:25:29And putting that all together.
01:25:31Right, that's what takes us
01:25:32an hour in the clinic.
01:25:33Right?
01:25:35That answer your question?
01:25:37Uh-uh. Not really. Yeah. Didn't
01:25:39it? Is a problem. Confused.
01:25:41I mean, if I have
01:25:41if it if if the
01:25:42melanomas reach my lymph nodes,
01:25:45is the course of action
01:25:46to take out all my
01:25:46lymph nodes or to put
01:25:48me on ipi or nebo?
01:25:50So should I I mean,
01:25:52to try to answer that.
01:25:53Okay. Yeah. So
01:25:54it first of all, things
01:25:56change
01:25:57over the period of our
01:25:58careers or the what the
01:26:00years that we've been doing
01:26:00that and more and more
01:26:01data become available. So what
01:26:03we did ten years ago
01:26:04is not what we did
01:26:04five years ago. What we
01:26:05do now is not exactly
01:26:06what we did five years
01:26:07ago either.
01:26:09So, you know, we have
01:26:10to take all of that
01:26:11into account. Now if the
01:26:13melon if the if there's
01:26:15nothing palpable,
01:26:17as doctor Lino says, if
01:26:18if this is microscope
01:26:32you start weighing the risks
01:26:33and the benefits. There is
01:26:34a ten percent or twenty
01:26:36percent depending on how big
01:26:37a person is and how
01:26:38many,
01:26:38and where where exactly the
01:26:40the lymph node basin is.
01:26:42But there's a risk for
01:26:43lymphedema
01:26:44long term.
01:26:45We always say, well, if
01:26:47we were going if the
01:26:48risk is high enough to
01:26:49justify giving adjuvant therapy that
01:26:51we just discussed, if we're
01:26:53going to give adjuvant therapy
01:26:54anyway, doing the surgery doesn't
01:26:56really add anything. So we
01:26:58may not go in and
01:26:59do the entire lymph node
01:27:00dissection. If we say we're
01:27:01not going in there to
01:27:03do adjuvant therapy for any
01:27:05reason, someone's got somebody's got
01:27:07an underlying disease, they we
01:27:08don't feel they can or
01:27:10should handle the immunotherapy,
01:27:12then maybe we would consider
01:27:13doing the nodal dissection. But
01:27:15what we know from at
01:27:16least three or maybe four
01:27:17surgical trials, correct me if
01:27:18I'm wrong, that in microscopic
01:27:21disease, just finding it in
01:27:22the central node and not
01:27:24doing a full nodal dissection,
01:27:25there's no difference in long
01:27:26term survival compared with monitoring
01:27:29it and if it does
01:27:30come back taking it out
01:27:31then.
01:27:32So
01:27:33early early lymph node dissection
01:27:35complete lymph node dissection versus
01:27:37late complete lymph node dissection
01:27:38does not impact survival.
01:27:40And particularly, if we're gonna
01:27:42be giving adjuvant therapy because
01:27:43then we're interfering with any
01:27:44potential cells that are there.
01:27:46Yeah. And if it's not
01:27:47microscopic I mean, I guess
01:27:48it sounds like the evolution
01:27:49is ipi and nivo is
01:27:50not a preferred path anymore.
01:27:53Ipi and nivo, we give
01:27:54if it's not microscopic and
01:27:56we can feel it Yep.
01:27:57And we don't wanna do
01:27:58a big surgery, we'll say,
01:27:59let's give a couple of
01:28:00cycles of ipi and nivo.
01:28:01No. That actually is what
01:28:02we've been doing in the
01:28:03last year. Okay. For stage
01:28:04three. For for big stage
01:28:06three, for bulky stage three
01:28:07that we can clearly feel
01:28:09and very high risk and
01:28:10a robust a robust patient.
01:28:13But we weren't doing that
01:28:14two or three years ago.
01:28:15That's a more recent development,
01:28:17the ipinivo.
01:28:19Taking it out and then
01:28:20doing epinevo, we don't do
01:28:21anymore. We tried, and it
01:28:22didn't didn't it didn't help.
01:28:24Yeah.
01:28:26Is that answer right now?
01:28:27That's a long answer. Okay.
01:28:29I'm happy to talk to
01:28:30you afterwards if you're like.
01:28:31Yeah. Go ahead. Yes. We
01:28:33have a question at the
01:28:34back there.
01:28:37Genius. And over the course
01:28:38of that period,
01:28:40the the the environment has
01:28:41really changed. Just watching this
01:28:43presentation
01:28:44was really amazing how much
01:28:45is happening.
01:28:47And my question as someone
01:28:49who's not in the medical
01:28:50scientific community, I read a
01:28:52lot of headlines.
01:28:54You know, the
01:28:55the current administration
01:28:57nationally that we're under is
01:28:58really cutting back funding in
01:29:01in research and science and
01:29:03cancer research specifically.
01:29:05Listening to Brandy talk about
01:29:07how amazing
01:29:09the hope and the the
01:29:10feeling of optimism she got
01:29:12coming here and being treated,
01:29:14I'm really curious.
01:29:15Thank you, Brandy.
01:29:17I'm really curious how what's
01:29:19happening in the political scene
01:29:21impacts the way you approach
01:29:23your job and and the
01:29:25research that's being done here,
01:29:26and if you're looking ahead
01:29:27and feeling hopeful.
01:29:30Yeah. So thank you for
01:29:31asking that question. That's a
01:29:32really charged one. And,
01:29:35if okay with everyone, I'm
01:29:36just gonna take a stab
01:29:37at answering it because you
01:29:39may you may get different
01:29:40answers from different people.
01:29:42We are worried. There's no
01:29:44question that we're worried about
01:29:45where the funding environment is
01:29:47going.
01:29:48We have had grants
01:29:50that were reviewed at the
01:29:51NIH that got top scores
01:29:53and and were not selected
01:29:55for funding
01:29:56in the last year for
01:29:57reasons that we we don't
01:29:59re they actually don't tell
01:30:00us, but things that wouldn't
01:30:01have happened two years ago
01:30:02or three years ago. However,
01:30:05with all of that, we
01:30:06have a really strong group
01:30:07here.
01:30:08And
01:30:10collectively, we actually still have
01:30:12a fair amount of funding,
01:30:13and we're very proud of
01:30:14that and grateful for that.
01:30:16Some of the funding comes
01:30:17from foundations like the MRA.
01:30:19We wanna thank them. The
01:30:20MRF is a different Melanoma
01:30:21Research Foundation, Melanoma Research Alliance.
01:30:24The Department of Defense has
01:30:26funded many of us, and,
01:30:27actually, doctor Ishizuka just got
01:30:29something from the NIH as
01:30:30well just a few weeks
01:30:31ago.
01:30:32So it we are we
01:30:34are seeing some funding coming
01:30:35in, and but we're still
01:30:36funded from older projects. So
01:30:38things that were submitted three
01:30:39years ago typically get funded
01:30:40for five years. We're still
01:30:41okay.
01:30:42The other beauty or advantage
01:30:44that we have here is
01:30:45that we work for Yale
01:30:46University,
01:30:47and we're very, very grateful,
01:30:50for that because there is
01:30:51a fair amount of of
01:30:53money within the system. And
01:30:54we have some,
01:30:55donors who've helped us a
01:30:57lot,
01:30:58in the last year. And
01:30:59now more than ever, we
01:31:00actually really are dependent on
01:31:02philanthropic
01:31:03donations.
01:31:04What we're hoping for is
01:31:05to ride out the wave
01:31:06until the NIH changes
01:31:09and things go back to
01:31:10where they are. But if
01:31:11anyone here wants to vote
01:31:13with their feet, please do
01:31:14so.
01:31:16We you know, but but
01:31:17the the the government does
01:31:19sometimes care about what people
01:31:20think. And the irony is
01:31:22that the sent the the
01:31:23house and the senate didn't
01:31:25actually cut the budget for
01:31:27NIH funding this year. They're
01:31:28just not dispersing the money.
01:31:29We don't know what they're
01:31:30doing with it, but it
01:31:31hasn't come into
01:31:33it hasn't come into this
01:31:34institution. So thank you so
01:31:35much for that question. I
01:31:36don't know if anyone wants
01:31:37to add to that. Maybe
01:31:38doctor Schonfeldt is someone who's
01:31:40also dependent on all of
01:31:41this.
01:31:42Thanks for including me.
01:31:45I don't know. No. I
01:31:47mean, I I I think
01:31:48you said it well, you
01:31:49know, doctor Kluger. I think
01:31:50it's concerning, and I think
01:31:51we're all worried because just
01:31:53the there's a lot about
01:31:54people to say the least.
01:31:55Yeah. I think that, you
01:31:55know, at least for the
01:31:56time being, things are very
01:31:57different than the way they
01:31:58used to be. And I
01:31:59think for the melanoma community,
01:32:01you know, there's still a
01:32:02lot to be done, but
01:32:03a lot of success. And
01:32:04we wanna continue on that
01:32:05track, and you can go
01:32:06even further and take it
01:32:07to the next level, and
01:32:08that's what we're all working
01:32:09on. So we're we're hopeful,
01:32:10and I think there's some
01:32:12many good things going on
01:32:13research wise. And funding wise,
01:32:15there's other sources like doctor
01:32:16Kluger mentioned between the foundations
01:32:18and philanthropy and still still
01:32:20some government funds, but I
01:32:21think we are worried and
01:32:22and just worried where things
01:32:23are heading overall. So
01:32:27Thank you for the question.
01:32:29Actual
01:32:30clinical trial?
01:32:34There are some
01:32:36so the neoadjuvant
01:32:37studies that doctor Olino talked
01:32:39about actually mostly came out
01:32:40of Australia and Europe.
01:32:43We do we do participate
01:32:45in them when we can.
01:32:47We may see more coming
01:32:48out of Europe because of,
01:32:50you know, because of funding
01:32:51cuts over here.
01:32:57Yes. Thank you.
01:32:59Slide on the four buckets
01:33:01for somebody who's not in
01:33:02the medical field. That was
01:33:03that helps kinda,
01:33:05separate the the, different,
01:33:07therapies.
01:33:09Did I understand right that
01:33:10you said, when you spoke
01:33:11about the immunotherapy
01:33:13that it has,
01:33:14more permanent response? It's more
01:33:16likely than that.
01:33:17And but yet more permanent
01:33:19side effects that would stay
01:33:21with could stay with the
01:33:22person.
01:33:23You know? I see. You
01:33:25know,
01:33:26diabetes
01:33:27and thyroid disease, etcetera, etcetera.
01:33:29So is that
01:33:31still of the four buckets,
01:33:32is that the number one
01:33:34place you go first? Or
01:33:36if you are BRAF positive,
01:33:38then you would go with
01:33:39targeted and then your secondary
01:33:41would be immune.
01:33:42So it was on doctor
01:33:44Chen's slide, the answer to
01:33:45your question. I'm gonna let
01:33:46her answer it though.
01:33:48Well, there was a lot
01:33:49there. We're not saying we're
01:33:50not having a standard.
01:33:53Wait. Wait. We we didn't
01:33:54cover this in clinic already?
01:33:58Just a few hours ago.
01:34:02So, really, it depends on
01:34:04the context.
01:34:05Right? If you have metastatic
01:34:07disease,
01:34:08then the chance of having
01:34:09a long term benefit and
01:34:11response
01:34:12and potentially even one day
01:34:14coming off of treatment entirely,
01:34:16if you have a complete
01:34:17response, meaning all the disease
01:34:19disappears on your scans, is
01:34:21higher with immune therapy.
01:34:23And so in those settings,
01:34:24sometimes a little risk outweighs
01:34:27or sorry. The
01:34:28the the benefits outweigh the
01:34:30risks in that scenario.
01:34:33With the targeted therapies, they
01:34:35work in the metastatic setting
01:34:38well for only so long,
01:34:40and then people relapse.
01:34:42It stops working. Resistance
01:34:44builds up, and then we
01:34:45start having to pivot again,
01:34:47talk about different therapies.
01:34:49When you're talking about stage
01:34:51three, though,
01:34:53they both have the same
01:34:54response
01:34:55in terms of decreasing
01:34:57relapse rates,
01:34:58but
01:34:59there is chance of a
01:35:01permanent side effect with the
01:35:03immune therapy that is not
01:35:05there with the targeted therapy.
01:35:07The targeted therapy also increases
01:35:10survival.
01:35:11So that's why in that
01:35:12stage three setting when we
01:35:14don't really know. Right? Are
01:35:16we doing you more harm
01:35:17or
01:35:18actually not providing any benefit
01:35:20with additional treatment? Technically, the
01:35:22tumor is out. The lymph
01:35:23nodes are out. There's no
01:35:25evidence of disease on the
01:35:26scans.
01:35:27And so to commit to
01:35:29something that could provide a
01:35:31permanent side effect,
01:35:33like type one diabetes,
01:35:35would be extremely detrimental because
01:35:37you maybe never needed that
01:35:38therapy at all.
01:35:40And so
01:35:41it depends on the stage.
01:35:43It depends on
01:35:45kind of personal decisions about
01:35:47the patient. This is why
01:35:48not everyone fits into the
01:35:50same mold. There's other variables.
01:35:52There's other lifestyle factors that
01:35:54we have to take into
01:35:55account
01:35:56to make sure that we
01:35:57personalize that decision and make
01:36:00the right decision
01:36:01as a group. You know,
01:36:02it's not what I recommend
01:36:04necessarily.
01:36:05It's what, like, the the
01:36:07where the values align in
01:36:09terms of improving long term
01:36:10patient outcomes
01:36:12and minimizing long term toxicity.
01:36:14Does that make
01:36:15sense? Okay.
01:36:18Okay. Necessarily, go for it
01:36:20first. Yeah. Just
01:36:22Thank you. So it's very
01:36:24interesting. In the past when
01:36:25we've had these symposia,
01:36:26all the questions were for
01:36:27the dermatologist,
01:36:30dermatologist, and he's just sitting
01:36:31there. So does anyone have
01:36:32a question for him going,
01:36:33going, going? Okay. Question is
01:36:35very good one. I mean,
01:36:35as in having had immunotherapy
01:36:38and the I
01:36:39personally haven't had any long
01:36:40term
01:36:41side effects. And not gonna
01:36:43move, but I think the
01:36:44cancer is out of me.
01:36:45And it was a lifesaver
01:36:46for me. But now it
01:36:47sounds like that's not as
01:36:49quick to be recommended course
01:36:50of action right now. Did
01:36:51I? And I is fascinating.
01:36:53One thing that was on
01:36:54doctor Tran's slide,
01:36:56and I think there was
01:36:57such an open question until
01:36:59four or five years ago
01:37:00for stage four, which is
01:37:02the same thing as metastatic
01:37:03disease, so a little different
01:37:04than than stage three, but
01:37:05whether one is better or
01:37:06not for these very issues.
01:37:07And so there was a
01:37:09specific trial that that doctor
01:37:10Tran mentioned that really
01:37:12was directly addressing that question
01:37:14in stage four patients, and
01:37:15there was such a wide
01:37:16gap in how patients did
01:37:18when they got immunotherapy first.
01:37:19So it really is what
01:37:21we go to if we
01:37:21can in in the stage
01:37:22four setting to where we
01:37:24think it really does make
01:37:25a difference if a patient
01:37:26can get immunotherapy.
01:37:27Yeah. And that trial was
01:37:29stopped early because they felt
01:37:30it was unethical to continue
01:37:32to give
01:37:33the targeted therapies first in
01:37:35stage four because the difference
01:37:36was so big.
01:37:41Any well, thank you all
01:37:43for coming. This was lovely
01:37:44and for the excellent questions.