Smilow Shares with Primary Care: Melanoma

Transcript

• 00:00Hello, Welcome to Smilo shares
• 00:03with Primary Care. I'm Karen Brown.
• 00:05I'm an internist in North Haven and the
• 00:08Medical Director of the Primary Care
• 00:10Service line of Northeast Medical Group.
• 00:13And I am joined normally to
• 00:16cohost this series with Ann Chang,
• 00:19who is not here and Kevin Billingsley,
• 00:22who's here and is the CMO of Smilo.
• 00:26We will introduce our speaker shortly.
• 00:28After an orientation to this
• 00:30session in general,
• 00:31today's topic is Melanoma.
• 00:33This is a monthly series designed to focus
• 00:37on primary care perspectives of cancer,
• 00:40especially diagnosis and handoff where
• 00:44we are involved and the designated
• 00:47audience is primary care clinicians,
• 00:50although I think many clinicians
• 00:52can learn from this.
• 00:53And we always have at least one
• 00:56primary care clinician along
• 00:57with SMYLO clinicians and often
• 01:00focused in one geography.
• 01:02This one is is not so much focused
• 01:05in one of our geographies and
• 01:08we hope that this will help us
• 01:10all become better at what we do.
• 01:12So we will go and we'll have a
• 01:15introductions and then we have
• 01:18a three case presentations.
• 01:21And we will learn through our
• 01:23case presentations and leave
• 01:24time for questions at the end.
• 01:29So at this time, I would like to introduce
• 01:32my NEMG primary care colleague, Dr.
• 01:35Flora Zarku Power Doctor.
• 01:39Zarku Power is a graduate of the University
• 01:42of Medicine Carol Davila in Bucharest,
• 01:44Romania, and she completed her
• 01:46internal medicine residency in New York
• 01:48Presbyterian Hospital in Queens, NY.
• 01:51She initially joined the staff of
• 01:54Yellow Haven Hospital as a hospitalist
• 01:56before starting her practice in Milford.
• 01:59She's now a practicing physician and
• 02:01also a managing partner of Primed,
• 02:03which is a PS:,
• 02:05A within Northeast Medical Group.
• 02:08She's been an active member of the Milford
• 02:10and Bridgeport area medical community,
• 02:12and she's been on the executive medical
• 02:15staff committee at Bridgeport Hospital.
• 02:17And is completing A2 year Emerging
• 02:19Leaders program through the
• 02:20Yale School of Management.
• 02:22She's an active clinical leader in
• 02:24Northeast Medical Group and lends
• 02:26her expertise to the NEMG Primary
• 02:28Care Steering Committee and also the
• 02:30Yale New Haven Health System Care
• 02:32Signature Pathway Work Doctor Zarku
• 02:34Power strongly believes in a patient
• 02:37doctor relationship as the keystone
• 02:40to great health outcomes and that
• 02:42a relational care team approach
• 02:45is paramount to effective care.
• 02:47Kevin,
• 02:47I'll turn it over to you on to introduce
• 02:50the members of yours Milo team.
• 02:53Karen, thank you.
• 02:55I'll just say it's really a
• 02:57pleasure for me to be here.
• 02:59I as you alluded to my associate Dr.
• 03:03Ann Chang generally partners with
• 03:05you in this wonderful venture.
• 03:08But I'm absolutely delighted
• 03:09and honored to be here.
• 03:11I'm a surgical oncologist and I service
• 03:14the Chief Medical Officer of the.
• 03:16Smilo Cancer Hospital
• 03:17and Health Cancer Center.
• 03:19And I will say on a personal note,
• 03:21I am just delighted to see
• 03:25this initiative moving forward.
• 03:27Those of us who are oncologists and
• 03:30are treating cancer patients regardless
• 03:32of our discipline are so indebted
• 03:35and tied to our primary care partners.
• 03:39It is really kind of the teamwork,
• 03:43the collaboration and the.
• 03:45The seamless flow of care between
• 03:49the primary care environment and the
• 03:51specialty environment that leads
• 03:53to great cancer care outcomes not
• 03:55only in the early diagnosis and in
• 03:57the support of the treatment phase,
• 03:59but in the survivorship phase.
• 04:01So I I think that this is really
• 04:05a valuable exercise and I'm.
• 04:07Hoping that that people are enjoying
• 04:10it and and taking a lot away from it,
• 04:13it's it's an honor for me to introduce
• 04:17several of my Smiley Smiley colleagues
• 04:19all of whom are esteemed experts
• 04:22in their field field and I'll I'll
• 04:26just start with Doctor Harriet Kluger.
• 04:29It would not be an exaggeration to
• 04:32say Doctor Kluger is a international
• 04:35authority in Melanoma and cutaneous oncology.
• 04:38She is the Harvey and Kate Cushing
• 04:40Professor of Medicine and the
• 04:42leader of the Melanoma program.
• 04:43Here at Smilow,
• 04:45she sees patients with both
• 04:47Melanoma and renal cell cancer.
• 04:49She has an extensive research portfolio
• 04:52with an interest in developing
• 04:54new drug regimens and biomarkers.
• 04:57That are predictive of response
• 04:59to therapy and Melanoma.
• 05:01She participates in a variety
• 05:03of clinical trials.
• 05:05She directs an active research
• 05:07laboratory that studies tumor and
• 05:09immune cells from patients treated
• 05:11with these novel therapies to
• 05:13determine mechanisms of resistance.
• 05:15Her laboratory also completes
• 05:17preclinical studies to improve treatment
• 05:19regimens for patients with Melanoma,
• 05:21renal cell cancer,
• 05:22and brain metestes.
• 05:26You know Harriet is definitely our go to
• 05:29expert and I think we'll find her just
• 05:32a fountain of knowledge in this regard.
• 05:35Next it's a pleasure for me to to introduce
• 05:37one of my surgical partners, Doctor Kelly.
• 05:40Olino Kelly is a W Board certified surgeon
• 05:43who provides patients comprehensive
• 05:45surgical care for skin and soft
• 05:48tissue tumors including Melanoma,
• 05:50markle cell cancer, sarcoma,
• 05:52basal cell cancer and others.
• 05:55She's been a recipient of a number of
• 05:58awards including the Society Surgical
• 06:01Oncologist Clinical Investigator award
• 06:03and she has funding through the Calabresi
• 06:06Immune Oncology Scholar program.
• 06:08She currently serves as the NCCN Non
• 06:12Melanoma cutaneous on the cutaneous
• 06:14malignancy committee and she's
• 06:16a great clinical surgeon.
• 06:19Next doctor Twee Tran.
• 06:20Twee is an assistant professor of Medicine.
• 06:24She cares for patients with
• 06:26Melanoma and other skin cancers at
• 06:28our spinal cancer hospital sites,
• 06:30both in New Haven and in Guilford.
• 06:34She is a graduate of the A/B IM Physician
• 06:37Scientist Research Pathway, and Dr.
• 06:40Tren is a bit of a a Yale product.
• 06:43She did both her internal medicine
• 06:46residency and her fellowship here at Yale,
• 06:49although she received both of her.
• 06:52Both her PhD and her MD degrees
• 06:56from Vanderbilt.
• 06:57She's also very involved in research,
• 06:59including novel therapeutics
• 07:01and drug combinations,
• 07:03and is a participant in the
• 07:06Yale skin Cancer spore.
• 07:08She's a principal investigator
• 07:11of several clinical trials.
• 07:13Last and certainly not least, Dr.
• 07:15Jonathan Leventhal is an associate
• 07:18professor of dermatology.
• 07:20And is the director of the
• 07:23SMILO Onco Dermatology Program.
• 07:26Doctor Leventhal received his
• 07:28bachelor's degree and medical degree
• 07:31at the NYU at NYU and then came here
• 07:34to Yale for additional training,
• 07:36where he served as a chief resident.
• 07:39His specialty is in providing care
• 07:42to skin cancer patients who develop
• 07:45cutaneous toxicities from their treatments,
• 07:47as well as diagnosing and treating
• 07:50skin cancers.
• 07:51Like many of the other panelists this
• 07:53evening, he leads clinical trials,
• 07:55studying new treatments for
• 07:57managing dermatologic toxicities.
• 07:59And he's actively involved in residency
• 08:02in medical education as well as
• 08:05serving as an editor for the textbook
• 08:07self-assessment in dermatology.
• 08:09So do you really have an
• 08:12outstanding cast of experts here?
• 08:14And I'll turn it back to you, Karen.
• 08:18Great. Let's get started. Florida,
• 08:21you want to present the first case.
• 08:23Karen, thank you for the warm introduction.
• 08:25I want to say your work
• 08:28and really unsailable.
• 08:29I'm probably then honored also to have
• 08:30the support of our colleagues. It's Milo.
• 08:33I'm going to start presenting the first
• 08:38case patient who came in reporting
• 08:41an enlarging leg mole situation that
• 08:43we encounter in practice quite often.
• 08:46I'm sure my colleagues will recognize it.
• 08:49This is a 59 year old healthy white
• 08:51female with a past mental history
• 08:53of hypertension hyperlipidemia.
• 08:54She has a history of having used
• 08:57tanning beds a few decades ago.
• 08:59She wasn't seen for about 3
• 09:01years due to a COVID pandemic.
• 09:04She reported a skin lesion about a year ago
• 09:07and notably enlarging her family history,
• 09:11is remarkable for her mother
• 09:14with a history of Melanoma.
• 09:16So I just wanted one more second
• 09:19probably to take a look at the lesions,
• 09:21so my colleagues could pay
• 09:22attention to some of the features
• 09:24that associate to this lesion.
• 09:28And we'll in a moment we'll discuss
• 09:31actually the ABCD's of recognizing
• 09:33the warning signs of Melanoma.
• 09:35So this would be sort of a
• 09:36a good picture to remember.
• 09:40We could move on to the next slide.
• 09:41So talking about moles and early signs
• 09:44of skin cancer, couple of specifics,
• 09:47what do we look for when we have a patient
• 09:50in front of us and we do a skin exam,
• 09:52we're looking for anything new or changing
• 09:55on both sun exposed and sun protected areas.
• 09:59Typically Melanoma appear in women
• 10:02on the legs and number one place
• 10:05they develop men is on the trunk.
• 10:08They could arise though anywhere on the skin,
• 10:10even in the areas where sun doesn't shine,
• 10:12so beware.
• 10:14Generally speaking, most moles,
• 10:15brown spots and growths on the skin
• 10:17are harmless, but not always.
• 10:22Here's the ABCDI was talking about.
• 10:25This is a simple guide to recognize
• 10:27the warning signs of Melanoma.
• 10:28A is for asymmetry, and if you draw a
• 10:31line through the middle of the lesion,
• 10:35the two halves don't match.
• 10:38B is for border.
• 10:39Typically they tend to be uneven.
• 10:42They may be scalloped or notched.
• 10:44C is for color.
• 10:46Multiple colors are a warning sign
• 10:48and melanomas may may have different
• 10:50shades of brown, tan, or black.
• 10:52D is for diameter.
• 10:54It is a warning sign if a lesion is larger
• 10:57than 6 millimeters or quarter of an inch,
• 11:00and any lesion that's darker
• 11:02than others not to be overlooked.
• 11:05One exception is the amylanotic melanomas,
• 11:08which are colorless,
• 11:10is for evolving any change in size,
• 11:14shape, color, or elevation of a spot.
• 11:17Any new symptoms of itching, crusting,
• 11:20bleeding, maybe warning signs?
• 11:23Also, look for an ugly duckling.
• 11:26The strategy is based on most
• 11:28malls resembling one another,
• 11:30while melanomas stand out
• 11:31like an ugly duckling.
• 11:40Jonathan, do you want to take over?
• 11:42Absolutely. It's a pleasure to be here,
• 11:44really happy to participate
• 11:45in Smile Shares Primary care.
• 11:47So I'm going to briefly highlight some
• 11:49of the main subtypes of a Melanoma,
• 11:52so superficial spreading as
• 11:53you can see on the top left,
• 11:55these are the most common types of Melanoma.
• 11:57You can see a lot of the features
• 11:59of the Abcd's from the last slide.
• 12:02And they tend to grow radially pretty
• 12:04slowly over the course of months to
• 12:07sometimes even years before then growing
• 12:09vertically and penetrating more deeply.
• 12:12Now this is in contrast to
• 12:13the nodular type of Melanoma,
• 12:15which tends to be far more aggressive
• 12:17and that these can grow quite rapidly
• 12:19and they tend to to present more deeply
• 12:22in the dermis at a higher stage.
• 12:24So these are important.
• 12:25You know,
• 12:26it's talking to patients about any
• 12:28recent change or rapidly growing skin lesion.
• 12:31The lentigo and malignant subtype
• 12:32tends to occur in elderly patients.
• 12:34Often looks like an atypical lentigo
• 12:37or a sunspot that elderly patients
• 12:39might develop in sun exposed
• 12:41areas but with atypical features.
• 12:43Probably the most challenging one
• 12:45for anyone to diagnose are the
• 12:48amylonotic types of Melanoma,
• 12:49and these tend not to have pigment,
• 12:51they're often pink and.
• 12:53Patient history can be very important
• 12:55here with a new amylonotic lesion
• 12:58that's either rapidly growing
• 12:59or symptomatic in some way such
• 13:01as being painful or bleeding.
• 13:03And then finally the acryl,
• 13:05intigenous and subungal types
• 13:07are important particularly in
• 13:08patients with darker skin types.
• 13:10They might be have a higher risk of
• 13:13developing this type and if that's
• 13:14why it's important when examining
• 13:16patients to look at the palms and soles.
• 13:18And regarding subungal Melanoma,
• 13:20these typically present with Melaninicia,
• 13:23which as you can see is a melanotic band
• 13:26that grows from the proxable nail upwards.
• 13:32I think it's important to have a
• 13:35differential diagnosis anytime
• 13:37you approached pigmented lesions.
• 13:40So I highlighted here on this
• 13:41slide what I think of as as
• 13:44the most clinically important,
• 13:45so I would say by far.
• 13:48The most common presenting diagnosis
• 13:50that that comes in with concern for
• 13:54Melanoma are seborrheic keratoses,
• 13:56which are on the the top left.
• 13:59These are stuck on waxy tan to brown
• 14:01or even darker brown black papules
• 14:03and plaques that tend to develop
• 14:06and patients as they get older,
• 14:08and sometimes they can be very challenging
• 14:11to distinguish from a Melanoma.
• 14:12So dermatologists use dermatoscopes.
• 14:14And if we are unsure,
• 14:16we'll perform a skin biopsy,
• 14:18certainly on the top right,
• 14:20we always consider normal appearing nevi
• 14:22and those that are slightly dysplastic.
• 14:25So they're not fully normal appearing.
• 14:28They might be slightly asymmetrical,
• 14:30borders are irregular,
• 14:31but these don't meet criteria for Melanoma.
• 14:34And when these are biopsied,
• 14:35they're not Melanoma then on the bottom left.
• 14:39Illustrates the fact that even non
• 14:41Melanoma skin cancers can be pigmented.
• 14:43So this is an example of a pigmented
• 14:45basal cell carcinoma noted as a slightly
• 14:48more pearly appearance to it and with
• 14:50a dermatoscope you might see other
• 14:52features of a basal cell on the the bottom.
• 14:55Middle picture is an example of vascular
• 14:59lesions such as angiokeratomas or angiomas.
• 15:02Sometimes they can have
• 15:03a really dark purplish,
• 15:04even blackish hue and can be challenging.
• 15:07As dermatologists,
• 15:08we can use a dermatoscope which
• 15:10you can see in the top right
• 15:12corner highlighting those vascular
• 15:13lacunae and that's reassuring.
• 15:15And then on the bottom right
• 15:17is a picture of a blue Nevis.
• 15:18And so these moles can also appear in
• 15:22as differential diagnosis of Melanoma,
• 15:25but they are benign.
• 15:29I just wanted to briefly
• 15:31review the epidemiology.
• 15:32Everyone here is familiar with Melanoma.
• 15:35I wanted to highlight that most
• 15:37cases actually occur on de Novo,
• 15:40although some might develop from
• 15:42a precursor lesion and these are
• 15:45typically either a congenital
• 15:46Nevis or an atypical Nevis that
• 15:48the patient has that then changes.
• 15:50It can occur in anybody,
• 15:52but tends to tends to predominant
• 15:55in white men over age 50.
• 15:57And then interestingly,
• 15:59underage 50 women outnumber men,
• 16:02likely due to tanning habits.
• 16:04It also is a diagnosis of young patients.
• 16:07And regarding survival,
• 16:08some factors associated with poor
• 16:10outcomes include elderly male patients,
• 16:13those who have darker skin types,
• 16:14likely because of the more
• 16:17aggressive biology and presentation
• 16:18of the equal indigenous Melanoma,
• 16:21as well as patients who are immunosuppressed.
• 16:25I very want, I very briefly wanted
• 16:27to provide an overview of the
• 16:29main risk factors for Melanoma.
• 16:30So like any cancer we can consider
• 16:33those that are environmental and those
• 16:35that are hereditary. Next slide.
• 16:39So for the environmental risk factors
• 16:41it's it's really all ultraviolet
• 16:43exposure and so we know that intermittent
• 16:46intense sun exposure throughout life
• 16:48and increase the risk of Melanoma.
• 16:49As well as sunburns,
• 16:51and not just childhood sunburns,
• 16:52but also sunburns that occur
• 16:54cumulative cumulatively through
• 16:56adolescence and adulthood.
• 16:57And finally,
• 16:58especially in young women,
• 17:00tanning beds have been associated
• 17:02with increased odds of Melanoma.
• 17:06And now I'll discuss some of
• 17:08the hereditary risk factors.
• 17:09So having decreased melanin and increased
• 17:12tendency to burn such as fair skin,
• 17:15freckling, blonde hair, red hair,
• 17:16light eyes are all associated with Melanoma.
• 17:19In addition, having an increased
• 17:21number of pigmented lesions,
• 17:22the important one here is having
• 17:24over 100 nevi that really increases
• 17:26the risk of developing Melanoma.
• 17:28And I think it's important to have
• 17:30an idea of these inherent risk
• 17:32factors because the United States
• 17:34Preventative Services Task Force does
• 17:36not recommend screening everybody,
• 17:37But it's important to keep in
• 17:39mind those who have phenotypic
• 17:41risk factors for Melanoma as well
• 17:43as personal or family history.
• 17:45Next slide.
• 17:48So having a history of skin
• 17:49cancer increases your risk of
• 17:51developing subsequent skin cancers,
• 17:53and this is true for Melanoma.
• 17:54As well as having a first
• 17:56degree relative with Melanoma,
• 17:57there are also genetic syndromes of
• 18:00kindreds who have Melanoma passed
• 18:02on from generation to generation.
• 18:04The most important one to know about
• 18:07clinically and the most common is the
• 18:10familial atypical multiple Melanoma syndrome.
• 18:12So these patients have hundreds of
• 18:14dysplastic appearing nevi and they're at
• 18:16increased risk of developing Melanoma,
• 18:18but also pancreatic cancer.
• 18:20And I think it's important to keep in mind
• 18:24who to think about screening for genetics.
• 18:27So we shouldn't send everyone
• 18:28who has a family history.
• 18:30So you want to keep in mind patients
• 18:32who have several members on one
• 18:34side of the family with a Melanoma
• 18:36or if a family member had more than
• 18:39one Melanoma and in particular.
• 18:41Anyone who comes from a family that has
• 18:43both Melanoma and pancreatic cancer,
• 18:45that should be an important clue.
• 18:48And we have seen many patients
• 18:50who have had several skin cancers,
• 18:52including melanomas.
• 18:53But you really want to think
• 18:54about those that have had over 3,
• 18:56three or more melanomas,
• 18:57especially if the first one
• 18:59happened when they were young.
• 19:01So I'm now going to turn it
• 19:02over to my wonderful colleague,
• 19:04medical oncologist Dr.
• 19:05Tran.
• 19:05To discuss how do we follow patients,
• 19:08especially those with low risk melanomas,
• 19:10Dr.
• 19:10Tran,
• 19:10thank
• 19:11you so much, Dr. Leventhal.
• 19:13So we typically see all Melanoma patients
• 19:15and follow up in medical oncology.
• 19:18And so we we typically follow these
• 19:20individuals for at least five
• 19:22years after their Melanoma surgery.
• 19:24Presuming that it's an early stage Melanoma,
• 19:26prognosis is typically very
• 19:28good with close surveillance.
• 19:29And we see these individuals,
• 19:31depending on their stage either every
• 19:33six to 12 months for the next five years
• 19:35and then subsequently at that point
• 19:37considered handing over the reins to
• 19:39primary care for ongoing surveillance.
• 19:41And every visit we check
• 19:43complete blood cell count,
• 19:45metabolic panel and an LDH as a
• 19:48surrogate tumor marker that we can
• 19:51assess for early Melanoma recurrences.
• 19:53And depending on the stage as well,
• 19:55for these early stage individuals,
• 19:57consider getting an either an
• 19:59annual chest X-ray or CAT scans.
• 20:01I think what's really important
• 20:03and helpful is that if the primary
• 20:06provider determines that there
• 20:08is any suspected new symptoms,
• 20:11any worrisome symptoms concerning
• 20:13for distant recurrence,
• 20:15we should always keep in mind to have a
• 20:18low threshold for ordering additional
• 20:20imaging and if possible for early diagnosis.
• 20:23After five years,
• 20:24and during that time as well,
• 20:26we always have to consider age appropriate
• 20:30cancer screening and continue full
• 20:32body skin checks with the dermatologist.
• 20:39I'll take over and I'll introduce case two.
• 20:42We are presented here with a 76 year
• 20:45old male who has a right forearm
• 20:48lesion noted about a year ago he denied
• 20:52any recent change in pigmentation of
• 20:54the lesion or rapid recent growth.
• 20:57He underwent a shave biopsy and
• 21:00pathology report revealed Melanoma,
• 21:02breast load thickness 2.3 millimeter.
• 21:06He reported a history of blistering sunburns.
• 21:09No history of tanning, but use.
• 21:12He does not have a history of Melanoma.
• 21:14His family history is also negative
• 21:15for Melanoma or non Melanoma,
• 21:17skin cancer and he retired from finance.
• 21:22On physical exam,
• 21:23he didn't have any evidence of
• 21:25lymphadenopathies and his skin exam
• 21:27on the biopsy site of the right
• 21:29forearm showed no signs of infection,
• 21:31no residual pigmentation,
• 21:32no nodularity, no satellite lesions.
• 21:36Next slide please.
• 21:38So this case,
• 21:40as you've heard earlier as
• 21:41Jonathan presented,
• 21:42is actually a nodular Type A lesion Melanoma,
• 21:50so.
• 21:50But this type requires a wide local
• 21:53excision to to treat the primary lesion.
• 21:55The probability of nodal
• 21:58micrometastasis is approximately 20%.
• 22:01The work up will include labs just X-ray,
• 22:04EKG if needed.
• 22:06Depending on the remainder of
• 22:09the history and lymphosyntography
• 22:11there is an indication for Sentinel
• 22:13node biopsy to determine staging
• 22:15and future therapy decision.
• 22:16In this case I'll turn it on to.
• 22:21Our colleague to discuss further.
• 22:24Hi,
• 22:24I'm Kelly Olina,
• 22:25one of the surgical oncologist and I have
• 22:28the pleasure to work with doctors Kluger,
• 22:30Tran and Leventhal on an everyday basis.
• 22:33So you know a lot of times when
• 22:35the patients first come in again,
• 22:36they come in really scared and that's
• 22:38really how we meet most people.
• 22:41They come in very uncertain.
• 22:43So again part of this is also to
• 22:45empower the primary care doctors
• 22:46on the line who know these patients
• 22:48inside and out and you know are more.
• 22:50More than just their doctors,
• 22:52you know, I think you guys really
• 22:53know the the person just as well as
• 22:56any doctor can know their patients.
• 22:57So, you know,
• 22:58when patients come in to see me,
• 23:00the first thing that we do is we,
• 23:01you know,
• 23:02we explain to them how the depth
• 23:04of their Melanoma really impacts.
• 23:06But there's certain principles
• 23:07that we stick to no matter what.
• 23:09So we talked about removing the Melanoma.
• 23:11We're not just removing the skin,
• 23:14we're removing the skin.
• 23:15We remove also the fatty tissue
• 23:17that that carries the lymphatics
• 23:19through which Melanoma cells.
• 23:20Can escape and it's actually based
• 23:23upon doing multiple trials that have
• 23:26been actually honed down studying
• 23:28thousands of patients over the year.
• 23:30Interestingly,
• 23:30in our attempts to make sure that the
• 23:33surgery becomes less and less morbid,
• 23:36we actually are now part of an
• 23:38international trial called the Melmark trial.
• 23:40So if any of your patients are coming in
• 23:42to see myself or Doctor Clune in our program,
• 23:45you may hear this,
• 23:46the mention of this trial.
• 23:47But again we're down to taking
• 23:49out about 1 to 2 centimeter.
• 23:51And that's really directly proportional
• 23:52to the depth of the Melanoma next,
• 23:58so you know. Laura had alluded to
• 24:02in this patient, you know we would
• 24:04strongly recommend you know this
• 24:06patient within the criterion of who
• 24:08benefits from having a Sentinel node.
• 24:10And again in these patients we do
• 24:12a full lymph node exam and when we
• 24:15do not detect any palpable disease,
• 24:17we then say do they have microscopic disease.
• 24:20Now just with any test that we would
• 24:22order if the patient isn't medically
• 24:24fit or if we're not going to act upon
• 24:27the additional staging information,
• 24:29I would never recommend that we
• 24:30do a procedure.
• 24:31Unless we're going to do
• 24:32something with that result.
• 24:33So for patients who have no high
• 24:36risk features in a thin Melanoma
• 24:38less than .8 millimeters,
• 24:40their lymph node risk is actually
• 24:41lower than the risk of the procedure.
• 24:44So we don't usually offer it in that setting.
• 24:47There's a newer indication of these
• 24:49in between .8 and 1 millimeter where
• 24:51we begin to have that discussion.
• 24:53But again, this continues to be a Gray area,
• 24:56the 1 to 4 millimeter.
• 24:58Range and even I would say the
• 25:00greater than 4 millimeter,
• 25:01I really do push patients because
• 25:03I do feel this information is
• 25:05incredibly important.
• 25:06There's some nomograms that you
• 25:08can direct your patients to or
• 25:09look up yourself Out of curiosity,
• 25:11one more mimics the population
• 25:12we see in Connecticut and that
• 25:14was developed from Memorial Sloan
• 25:16Kettering is now almost 20 years old.
• 25:18The other one is from Australia, however.
• 25:19Melanoma in Australia is a little
• 25:21bit different than what we see
• 25:23in the United States,
• 25:24so again I usually have people
• 25:26take a look at both,
• 25:27but it gives them kind of an
• 25:30idea where their risk is next.
• 25:32When we talk about what a
• 25:33central node biopsy is,
• 25:34again some principles really
• 25:36overlap with that of breast cancer.
• 25:39However, each one of us is completely unique.
• 25:42And I tell patients all the time,
• 25:43if you don't know where you're going,
• 25:44you need a map to get there.
• 25:45So that's what the lymphocentigraphy is.
• 25:48So we inject 2 dyes,
• 25:49one's a blue dye and the other one
• 25:51has a little bit of technetium.
• 25:53So it's got a little bit of
• 25:55radioactivity that's completely saved
• 25:56out of the system within six hours.
• 25:58And what that does is it tells me
• 26:00which nodal station to look for, so.
• 26:01In this case,
• 26:02it's right in the middle of the belly.
• 26:04And again,
• 26:05because we're looking for
• 26:06microscopic disease,
• 26:07we have to figure out where to go.
• 26:08And then what we do in the operating
• 26:10room is we have a little handheld
• 26:12Geiger counter and that really
• 26:13helps me hone in on which of the
• 26:15lymph nodes to remove next and
• 26:18why is that so important click.
• 26:22That's because it is still
• 26:25our best prognostic value in.
• 26:28Looking at recurrence and death from
• 26:30Melanoma and this was one of the most
• 26:32remarkable trials that's been done
• 26:33in the field of surgery for Melanoma.
• 26:36So even though it's an additional surgery,
• 26:38it gives us still more valuable
• 26:40information than that of some of these
• 26:43gene expression profile arrays that you
• 26:45may also have patients come in with next.
• 26:49And we used to actually take out all of
• 26:51the lymph nodes when we had patients who
• 26:54would even have microscopic disease.
• 26:56However, there were two trials,
• 26:57one in Germany and 1 multicenter in
• 27:00the United States that showed that
• 27:03doing this additional surgery did
• 27:05not improve a patient's survival
• 27:08specifically with their Melanoma survival.
• 27:11So what we do is we.
• 27:13We remove lymph nodes only if someone
• 27:15comes in and we can actually feel
• 27:17the lymph nodes and then there's
• 27:19some more selection criterion that
• 27:20would be a little bit more unusual.
• 27:22And again,
• 27:23the important thing is we actually
• 27:26now have effective treatments.
• 27:28So I'll next slide,
• 27:31so Doctor Tran will talk a little
• 27:33bit about this about what we
• 27:35call adjuvant immune therapy,
• 27:37which is a conversation that
• 27:38many of our patients now have.
• 27:42So as Doctor Alina had already discussed,
• 27:45one of the key decisions here is you know
• 27:48whether to pursue Sentinel lymph node biopsy.
• 27:51And so my next part is kind of talking
• 27:54about what how can we move the needle
• 27:57further decrease recurrence risk in
• 27:58these patients who may have a positive
• 28:01lymph node or otherwise thickened
• 28:03melanomas or ulcerated melanomas which
• 28:05have a higher risk for recurrence.
• 28:08And so this this chart just kind of
• 28:11displays for the five year Melanoma
• 28:13specific survival for the higher risk
• 28:15stage twos which are included two B's and
• 28:18two C's as well as the stage 3 melanomas.
• 28:21And as you can see there are actually some
• 28:24subsets of stage 3 melanomas that do much
• 28:26better than the higher risk stage two events.
• 28:29So for stage 3A melanomas,
• 28:31the five year Melanoma
• 28:33specific survival is 93%.
• 28:35And so compare that to a stage 2C where
• 28:38the where that survival decreases to 82%.
• 28:42So when you talk about
• 28:44adjuvant immune therapy,
• 28:45we're always talking about one additional
• 28:47year of some sort of systemic treatment
• 28:50either in the form of immune therapy
• 28:53or targeted therapy with the goal of
• 28:56trying to decrease recurrence risk.
• 28:58So in terms of adjuvant, oh,
• 29:00I'm sorry, if you could go back.
• 29:03In terms of adjuvant immune therapy options,
• 29:05there are two FDA approved drugs,
• 29:07temporalismab also known as Keytruda
• 29:09which is given every three to six weeks
• 29:12versus new volume M also known as Opdiva
• 29:15which is given every two to four weeks.
• 29:18Again these are all intravenous,
• 29:20they have similar side effect profiles
• 29:23and they both target the PD1 protein.
• 29:25To help stimulate the immune
• 29:28response against Melanoma.
• 29:29Both of these drugs are considered
• 29:33interchangeable in stage 2 Melanoma and
• 29:35as well as stage 3 melanomas In general,
• 29:38it's been known to have a decrease of 40%.
• 29:42In terms of the recurrence,
• 29:43however, there is no impact upon
• 29:47improving survival to date.
• 29:49Next slide.
• 29:51As an alternative to immune therapy
• 29:53for individuals with a B RAF mutation,
• 29:56mainly V600E or V600K mutations,
• 30:00which are present in about
• 30:02half of cutaneous melanomas,
• 30:03there is additional alternative
• 30:06adjuvant therapy in the form of B,
• 30:09RAF and MECH inhibitors,
• 30:10so drabrafnib and tremet NIB,
• 30:12which are both oral medications.
• 30:15Either given BID or daily respectively.
• 30:18And these medications are approved
• 30:20not in the stage 22 setting,
• 30:22but in the stage 3 setting for individuals
• 30:25with lymph node positive Melanoma,
• 30:28where it's been shown to
• 30:30reduce recurrence risk by half.
• 30:32But unlike immune therapy,
• 30:34it has been demonstrated to
• 30:36impact overall survival as well.
• 30:38Next.
• 30:41So for these individuals
• 30:42with higher risk melanomas,
• 30:44we typically again follow
• 30:45them closely for five years,
• 30:48but because of our higher
• 30:49risk for recurrences,
• 30:50we see them more frequently and we also
• 30:53do imaging more frequently as well.
• 30:55And these imaging can typically
• 30:57include a CAT scan of the chest,
• 30:59abdomen,
• 31:00pelvis.
• 31:00And I think the main point very
• 31:03similar to early stage melanomas
• 31:04is that as a primary care
• 31:06physician, it's always.
• 31:08Very helpful to screen these
• 31:10patients for any atypical symptoms,
• 31:13red new red flag symptoms because
• 31:15again if we can detect these,
• 31:17if we can diagnose these earlier
• 31:20outcomes are much better potentially
• 31:22if it's localized recurrences,
• 31:24they can still undergo A
• 31:26potentially curative resection.
• 31:28The most important thing even after
• 31:30five years is that these individuals
• 31:32still see the dermatologist still have
• 31:34age appropriate cancer screening.
• 31:36And while we only see these individuals
• 31:38for five years in medical oncology,
• 31:42it's so important to keep a
• 31:44low threshold for additional
• 31:45work up if there's any concern.
• 31:47And so the graph at the bottom here
• 31:49is just a representative graph from
• 31:52the adjuvant trials of Jabrachno
• 31:54Ventremett showing that at 60 months
• 31:57which is equivalent to five years
• 31:59although the recurrences plateau.
• 32:01There is still a few recurrences
• 32:04afterwards and so even despite completing
• 32:065 years without any recurrence of disease,
• 32:10there's still a possibility and so that
• 32:12has to be something that is factored in,
• 32:15particularly if a patient
• 32:16develops new symptoms,
• 32:17New lymph adenopathy next.
• 32:23So when we talk about individuals
• 32:24with high risk disease,
• 32:26adjuvant therapy isn't the
• 32:27correct answer for everyone.
• 32:29We have to individualize the and
• 32:32personalize these decisions based on age,
• 32:35comorbidities, what stage they are,
• 32:37going back to the fact that some stage
• 32:40threes act even better than some stage twos.
• 32:43Also the risk of toxicities as
• 32:46well immune therapies can often
• 32:48times lead to permanent toxicities,
• 32:50endocrinopathies that require lifelong
• 32:53hormone replacement or steroid replacement
• 32:56for example versus reversible toxicities,
• 32:58more so in the case of oral targeted
• 33:02therapies with B raft neck inhibitors.
• 33:06We also have to factor in quality of life
• 33:08as well with some of these side effects.
• 33:11And then whether or not all of this is
• 33:14and what we're doing makes any impact
• 33:16in terms of how long people live,
• 33:18which is our ultimate endpoint.
• 33:21We have some interesting upcoming
• 33:23clinical trials here that many of
• 33:26you might have heard in the news.
• 33:28We will be opening the phase three
• 33:30portion of our personalized mRNA
• 33:32vaccine for Merck in combination with
• 33:35pembrolizumab that has been shown to
• 33:37reduce further the recurrence risk.
• 33:41In high risk melanomas.
• 33:44And so that it will be something that
• 33:45would be opening up in the next few months.
• 33:47And we also have additional
• 33:49trials of antitigit antibodies
• 33:51in the adjuvant setting as well.
• 33:53So really potentially interesting clinical
• 33:55trials coming down the pipeline. Next
• 34:01I'll take over from here and
• 34:04we'll talk about another case.
• 34:05This is a 73 year old male
• 34:08presented who with a left sided
• 34:10cervical lymphadenopathy.
• 34:11A CAT scan of the neck was ordered
• 34:14to further work this up and it
• 34:18showed 4 enlarged centrally necrotic
• 34:21lymphadenopathies lymph nodes.
• 34:23Biopsy of the left scalp lesion
• 34:26revealed a Melanoma.
• 34:29An ultrasound guided biopsy
• 34:30of the left cervical node was
• 34:33positive for metastatic Melanoma.
• 34:35He subsequently underwent white local
• 34:37excision of the left parietal scalp
• 34:39lesion and the patch revealed metanoma
• 34:41and cyto and scar with negative margins.
• 34:46Left neck lymph nodes were excised
• 34:48and three out of 10 are positive
• 34:52for metastatic Melanoma.
• 34:53Next line he subsequently presented
• 34:57to ER with generalized abdominal pain,
• 35:00nausea,
• 35:00vomiting and diarrhea for three days.
• 35:03The CT of the other men and
• 35:05pelvis show liver metastasis,
• 35:06peritoneal carcinomatosis and bowel
• 35:08obstruction with antisusception
• 35:10and mass of the transition point.
• 35:13He underwent surgery ilial bowel resuction
• 35:17of metastatic Melanoma and anastomosis.
• 35:20Subsequently he developed
• 35:22symptoms of dizziness.
• 35:24MRI of the brain performed
• 35:27showed 49 to predatorial and
• 35:2914 in predatorial lesions.
• 35:34Next time I'll
• 35:37turn it to my colleague.
• 35:39Thank you, Flora. So when we
• 35:42talk about metastatic Melanoma,
• 35:44people generally feel, oh, it's stage 4,
• 35:47it's a terrible prognosis.
• 35:48We're actually within the last 20 years,
• 35:51we've had a lot of new targeted
• 35:54therapies and immune therapy
• 35:56combinations that have sort of changed
• 35:59the paradigm for how we think about.
• 36:01Stage 4 disease, historically 5
• 36:04year survival has been very dismal,
• 36:07but that is ongoing in terms of
• 36:10improvements within the last few decades.
• 36:13So in the middle here we have sort of
• 36:16an outline of the recent drug approvals
• 36:20that include now immune therapy,
• 36:23combinations of immune therapy in the
• 36:26systemic setting for metastatic disease.
• 36:29Which is which are all labeled
• 36:31above the the timeline bar there.
• 36:33And to even add on to this and give
• 36:36give a quick update within the last
• 36:39year two additional new treatments
• 36:42were are also approved as well.
• 36:44So when we talk about metastatic
• 36:47Melanoma combinations of the
• 36:49Lumumab and Volumeab are now having
• 36:52demonstrated objective responses
• 36:54rate response rates of around 58%.
• 36:57Which is astounding.
• 36:58So this means patients that
• 37:00respond have stable disease or
• 37:03even complete responses as well.
• 37:05There are multiple treatment options
• 37:07that we can try for these individuals,
• 37:09some of them more tailored to certain
• 37:12subtypes of Melanoma such as UVL melanomas,
• 37:16but overall,
• 37:17really kind of changing the paradigm here.
• 37:21When we talk about immune therapy,
• 37:23which is intravenous versus targeted therapy,
• 37:26which is oral,
• 37:28really the individuals that can only
• 37:30benefit from the targeted therapies are
• 37:32the ones with activating the graph mutations.
• 37:35And so that's only a smaller
• 37:37subset of individuals.
• 37:39And when we talk about sort of what
• 37:41is the correct sequence of therapies,
• 37:44this is has been recently addressed
• 37:46in the DREAM SEEK trial and we now
• 37:49know that frontline immune therapy
• 37:50is superior to targeted therapy in
• 37:53terms of multiple factors including
• 37:55overall survival,
• 37:56progression free survival and the
• 37:58duration of response to treatment
• 38:00as well
• 38:03next so. Immune therapy can
• 38:06cause multiple different types
• 38:08of immune related toxicities,
• 38:10which my colleague Dr.
• 38:11Kluger will detail for us now.
• 38:15Thank you Doctor Tran.
• 38:16So everything comes with
• 38:18the price unfortunately.
• 38:19So these immune therapies are wonderful
• 38:21in that not only do they induce response,
• 38:23but these response can be these responses
• 38:25can be durable and last for many, many years.
• 38:28We have many patients who are
• 38:30alive and well over a decade after
• 38:33stopping the immunotherapy.
• 38:34The other advantage to the immuno?
• 38:35Therapies that you can treat for a
• 38:37certain period of time and then stop,
• 38:38they're not on continuous therapy,
• 38:41but the the price to pay is the
• 38:43immune related adverse events.
• 38:45So if you think about the mechanism
• 38:47by which these drugs work,
• 38:48it's not really specifically
• 38:50targeting the cancer cells.
• 38:51So we stimulate the immune
• 38:53system in a nonspecific way,
• 38:54but we also have T cells that
• 38:57recognize our normal organs
• 38:59that are that are quiescent.
• 39:02By various mechanisms and they are,
• 39:04they remain that way during our
• 39:06our lifetime but they they live
• 39:08there as resident memory cells.
• 39:10So these these cells actually live
• 39:12in almost all organs in our body.
• 39:15And when we inhibit the breaks on
• 39:16these cells with immunotherapies
• 39:18that we administer,
• 39:19you then can get inflammation
• 39:21in almost any organ in the body.
• 39:23The common ones are the hormonal
• 39:27side effects,
• 39:29colitis and respiratory problems.
• 39:31Now some of them are quite
• 39:34reversible with very responsive to
• 39:36immune to to immune suppression,
• 39:38specifically steroids and sometimes they
• 39:39resolve quite quickly when we give steroids,
• 39:42others may remain permanent.
• 39:43So for reasons that we still don't
• 39:46quite understand the endocrine
• 39:48toxicities are never reversible.
• 39:49Diabetes or type one diabetes
• 39:51can be fulminant,
• 39:52it's quite rare,
• 39:53less than 1% but very difficult to control
• 39:56and certainly a life altering event.
• 39:59Hyperpituitism occurs in around 15%,
• 40:02that's one 5% of our patients.
• 40:05And if you think about a patient who
• 40:06might be cured with surgery alone,
• 40:08receiving immunotherapy in the adjuvant
• 40:10setting causing pituitary insufficiency
• 40:13as a lifelong toxicity certainly
• 40:15can affect them for decades to come.
• 40:18And these patients are at risk when they
• 40:20when they get sepsis or undergo surgery.
• 40:22So if you have any of those in your practice,
• 40:24please keep in mind that they need stress,
• 40:27those steroids if they ever get sick.
• 40:30Sometimes the neurotoxicities and the
• 40:32cardiac toxicities are also irreversible.
• 40:35The death rate from the immunotherapy
• 40:37is quite a bit less than 1%,
• 40:39but sadly we've all had a death
• 40:41and it's something that does occur
• 40:43regardless of how careful we are.
• 40:45The other problem that we have is
• 40:47that we have no means by which we
• 40:49can predict who's going to develop
• 40:51the toxicities and who won't.
• 40:52There are a number of immune
• 40:55suppression approaches that we use.
• 40:57They listed over here on the
• 40:59right primarily steroids,
• 41:01but I think this field is undergoing
• 41:03rapid evolution and I believe that
• 41:05in the next 5 to 10 years we'll be
• 41:08using an array of different immune
• 41:09suppressants that might be more specific.
• 41:13To the the resident memory cells
• 41:16rather than the anti
• 41:17cancer immune cells.
• 41:19So more to come on that as we go as
• 41:22we proceed into the next decade.
• 41:25Next slide please.
• 41:25So the next question is what do
• 41:27we do about patients who have
• 41:29underlying autoimmune disorders.
• 41:30So I think all primary care folks
• 41:32have many patients in their practice
• 41:35who carry a diagnosis of RA,
• 41:36Polymyalgia, Rheumatica and the like.
• 41:39And I think that sometimes
• 41:40these diagnosis were made many,
• 41:42many years ago,
• 41:44disease can possibly burn out with time.
• 41:47But we have been successful in treating
• 41:50some of these patients with immune therapy.
• 41:53It's it's challenging often
• 41:55we need to pay extra,
• 41:58extra attention to these folks but
• 42:00certainly if they have an underlying
• 42:03autoimmunity that's not life threatening,
• 42:06the immunotherapy can be administered.
• 42:09Quite safely.
• 42:09I do specifically want to draw your
• 42:11attention to inflammatory bowel
• 42:13disease because it's increasing
• 42:14in incidence and that is actually
• 42:16particularly challenging for us because
• 42:18patients actually can die of bowel
• 42:20perforation if we're not careful.
• 42:22It doesn't mean we can't do it.
• 42:24We can give therapies that are active
• 42:26specifically in the bowel such as
• 42:28veto lizumab and sometimes we are
• 42:30very successful with that and can
• 42:32induce a long term cancer remission.
• 42:35Next slide please. Thank you.
• 42:37So lastly, but certainly not least,
• 42:42brain metastases in Melanoma
• 42:43is a big problem for us.
• 42:45Approximately half of our patients
• 42:47who have metastatic disease develop
• 42:50brain metastases at some point in the
• 42:52course of their illness and they can
• 42:54sometimes present with brain metastases
• 42:56as the first site of metastatic disease.
• 42:58So they'll present with.
• 43:00Headaches, neurologic problems,
• 43:01et cetera.
• 43:02The tip off is that the headache
• 43:04is worse when they lie down.
• 43:06It gets better over the course of the day.
• 43:09The headaches can be
• 43:10severe as the tumor grows.
• 43:12One can have a Mass Effect
• 43:15midline shift and the
• 43:16one thing that Melanoma
• 43:18brain metastases.
• 43:20Unfortunately, do is is is hemorrhage.
• 43:24So other than many other tumor types,
• 43:27these are more prone to hemorrhage.
• 43:28And there's a lot of Peri lesional
• 43:31edema around these lesions,
• 43:32possibly more than in other tumor types.
• 43:34And it's the edema itself that can
• 43:36actually cause problems and actually
• 43:39Doctor Tran has done a lot of.
• 43:41Research on this topic in particular,
• 43:44there are better treatments available.
• 43:46We've got effective systemic
• 43:48therapies for brain metastases.
• 43:50We believe that immune therapies,
• 43:52when they work in the body,
• 43:53they're going to work in the brain as well.
• 43:55But sometimes we have complications such as
• 43:57the edema and resultant symptoms from that.
• 44:00These lesions can be Gamma
• 44:02Knife with radiation therapy,
• 44:04or they can simply be treated
• 44:07with systemic therapy.
• 44:08We tailor individual treatment plans
• 44:10to all of these patients because
• 44:11brain metastases are not alike.
• 44:13Some patients may have one big one,
• 44:15while others, well,
• 44:16they can have many small ones.
• 44:17Some have hemorrhagic lesions,
• 44:19some have lesions that cause a lot of edema.
• 44:24So this arena as well is an area
• 44:26of very active research at Yale.
• 44:31I'm going to turn it back to
• 44:32Doctor Tran to talk about the
• 44:35conclusions and the major takeaways.
• 44:39So I think Doctor Kluwe,
• 44:41you highlighted on a lot of these
• 44:44and very important side effects
• 44:46that it would be important for our
• 44:49primary care colleagues to know about.
• 44:51We are typically very aggressive about
• 44:53treating these individuals metastatic
• 44:55Melanoma with immune therapies.
• 44:57Sometimes we do seem like we
• 44:59push them to be able to receive.
• 45:01Their treatments only because we
• 45:03know based on experience that if if
• 45:06they're able to attain a response
• 45:09with immunotherapies that response
• 45:10can be profound and longlasting.
• 45:13But unfortunately what happens during
• 45:15the course of the this treatment
• 45:17is a lot of lifelong toxicities can
• 45:19develop which we need our primary
• 45:21care colleagues to be aware of
• 45:23and to have a low threshold about
• 45:26helping us to Co manage them.
• 45:28So things like adrenal insufficiency
• 45:30in patients who are presenting
• 45:32with a Uri symptoms,
• 45:34they need to be stressed,
• 45:35dosed and sometimes we can avert
• 45:37hospital admissions if the patient and
• 45:39the primary care physician are aware
• 45:42that tunes to this potential side
• 45:44effect also and as Doctor Kluber alluded to,
• 45:48you know diabetes.
• 45:49These type one diabetes that can
• 45:51develop on immune therapy are very life
• 45:55changing and require multidisciplinary
• 45:57care with endocrinology and primary
• 45:59care to help manage thyroiditis is
• 46:01sometimes one of the side effects that
• 46:04we can see that perceives hypothyroidism
• 46:06in these patients depending on how
• 46:09frequently we check the the TSH levels.
• 46:11I think one of the also the important.
• 46:14Facts that as a primary care physician,
• 46:18if you have a patient that you know
• 46:19who is on immune therapy presenting
• 46:22with extreme fatigue,
• 46:23one check for the endocrine potential
• 46:25side effects but also make sure that
• 46:28they aren't having myocarditis too.
• 46:30If you know or you suspect our toxicity,
• 46:34please let us know.
• 46:35Reach out to us, we're happy to be involved.
• 46:38We don't expect primary care to
• 46:41manage the toxicities acutely,
• 46:42but just letting us know how helps
• 46:46us to determine what treatment,
• 46:48you know,
• 46:49is indicated for the individual
• 46:51toxicities at hand.
• 46:52And a lot of the times even though
• 46:55patients may develop a toxicity,
• 46:56it's actually might be a good sign
• 46:59that maybe their immune system is
• 47:01being activated and potentially will
• 47:03produce the anti Melanoma response.
• 47:06So we've seen correlations between
• 47:09very severe toxicity toxicities and
• 47:11very good responses in our patients.
• 47:14So in terms of treatment assessments,
• 47:16so going back to the case in hand,
• 47:19this gentleman who Doctor Lena and
• 47:21I treated with metastatic Melanoma.
• 47:23He was treated with a combination
• 47:26of ipilumab and uvalumab.
• 47:28And after the first four cycles,
• 47:30so looking at his scans,
• 47:32pretreatment on the left and then
• 47:34on treatment after four cycles,
• 47:37there is a dramatic improvement
• 47:39in disease tumor burden both in
• 47:41the brain and in the body.
• 47:43Typically with immune therapies
• 47:45these responses are concordant
• 47:47because these are known to be
• 47:50brain active treatments as well.
• 47:52Early on though,
• 47:53if you do happen to come across a
• 47:55scan for a patient on immune therapy,
• 47:57just be wary that pseudoprogression
• 48:00can exist in these patients on early
• 48:03scans whereby the tumors may look
• 48:05bigger on imaging, but actually not
• 48:08be a full real tumor progression,
• 48:11but actually just radiographing
• 48:13enlargement from the infiltration
• 48:15of activated immune cells.
• 48:17Clinically, we can sometimes determine
• 48:19pseudo progression because the
• 48:21patient otherwise is doing well,
• 48:23they don't have any symptoms and if the
• 48:27degree of enhancement is not significant,
• 48:30then sometimes we will push these
• 48:33patients continue treatment and
• 48:34then confirm with restaging later
• 48:36on whether or not they had pseudo
• 48:40progression or true progression.
• 48:42So patients are able to eventually.
• 48:46In a subset of folks obtain
• 48:48complete responses,
• 48:49basically almost a curative response
• 48:52to their systemic immune therapy
• 48:54and sometimes patients are able to
• 48:56stop and have ongoing responses
• 49:00next. So just to close out the
• 49:04take away points from today's
• 49:05presentation is you know
• 49:07early detection is critical.
• 49:09And that's where you know all
• 49:11hands on deck are appreciated,
• 49:13primary care's involvement and
• 49:15doing ongoing surveillance,
• 49:17looking at the scar,
• 49:18checking the patient's lymph nodes,
• 49:20assessing for any unusual atypical symptoms.
• 49:24Because early detection is always important
• 49:26in terms of improving ultimate outcomes,
• 49:29and everyone plays a role
• 49:31in the surveillance.
• 49:32It's a truly multidisciplinary,
• 49:36multiexpertise kind of approach here.
• 49:40So aggressive upfront Melanoma
• 49:42management and treatment,
• 49:44as we always said,
• 49:45leads to improve outcomes not only
• 49:47for the patient but also to help
• 49:49minimize potential toxicities as well.
• 49:53Fortunately, we've lucky enough to
• 49:55work in a field where therapeutics
• 49:57are always improving and we've
• 49:59been at the forefront of helping to
• 50:01push that boundary forward with the
• 50:03ongoing clinical trials here at Yale.
• 50:06And the number of patients that are
• 50:08living with a history of Melanoma is ever
• 50:11growing and we owe that and thanks to.
• 50:14The drugs but also the close corroboration
• 50:17that we have between or specialty
• 50:19with in Melanoma but also with
• 50:22ongoing primary care physicians too.
• 50:26That was absolutely terrific.
• 50:30Thank you for all of that.
• 50:34Those who are watching please
• 50:37submit questions using the Q&A
• 50:40because we we do have some time.
• 50:43Left over and you know I just
• 50:45have to say as a mature primary
• 50:48care physician that the change in
• 50:51prognosis for advanced Melanoma
• 50:53is one of the most miraculous
• 50:56things I've witnessed clinically.
• 50:57So it is amazing and it it's just
• 51:01nice to hear that whole kind of
• 51:04evolution outlined although not
• 51:05without a price as we as we've heard.
• 51:10As we wait for some questions to come
• 51:11in and and those who are watching,
• 51:13please do submit questions.
• 51:16Flora, do you have additional
• 51:18questions for our Smilo panelists?
• 51:21So sure, a basic question.
• 51:24When we are dealing with a patient in
• 51:26the office who we suspected toxicity,
• 51:28what's the shortcut?
• 51:30What's the the easiest way and
• 51:33fastest way as well most effective
• 51:35to get in touch with with the
• 51:37team caring for this patient.
• 51:40So we have one phone number that's
• 51:45to 203-200-6622.
• 51:46We make sure that all patients who start
• 51:49immunotherapy put that on speed dial.
• 51:52Someone answers that phone
• 51:5424/7 during work hours.
• 51:56They can send a message in my chart.
• 51:58It goes straight to our nursing pool,
• 52:00but depending on the urgency,
• 52:02they may decide to call.
• 52:05And whether they seen in Guildford
• 52:06or in New Haven, they the phone
• 52:08calls for urgent issues such as
• 52:10that would come into New Haven.
• 52:14Thank you.
• 52:17And I'll just add on to that.
• 52:19When we have somebody, you know,
• 52:21with a skin lesion in primary care,
• 52:23we have ones that are like we
• 52:25can't really tell you it's normal.
• 52:27And then we have ones that like look
• 52:29like they might be a problem and then
• 52:30they have ones that that scream at us.
• 52:32This person absolutely needs this remove.
• 52:34Right away and delaying care is not good.
• 52:38You know within the kind of Yale system,
• 52:41what are some of the most efficient ways
• 52:43that we can kind of help to navigate
• 52:45and and refer those type of people.
• 52:49Sure. I can take this one.
• 52:50Well, I think you know we have many
• 52:53dermatology services outpatient
• 52:55all all throughout New Haven
• 52:57and Brantford and Middlebury.
• 52:59I think putting in an urgent referral.
• 53:01I think what what often helps is calling
• 53:03the office also just to leave a message.
• 53:05We're really worried about this one.
• 53:07A lot of primary care doctors will
• 53:09send me an epic and basket message.
• 53:11Can you please get this patient
• 53:12in soon with you or a colleague,
• 53:13We're really worried about this one.
• 53:15I think that sort of triage is is helpful.
• 53:17We also have telemedicine to
• 53:19look for urgent lesions,
• 53:21but I'm I'm more of a proponent of seeing
• 53:24the the patient in in person to examine it.
• 53:27So we can use a dermatoscope and biopsy
• 53:32and then doctors are power
• 53:35actually alerted me as to these.
• 53:37Little things I I use them in the garden.
• 53:39When I see a weed or something that I
• 53:41think might be a weed or maybe the plant
• 53:43I planted last year and forgot about,
• 53:45I I use this identify thing and it
• 53:47tells me exactly what the plant is.
• 53:50Is there a software that can help us?
• 53:52You know, there's a lot of new
• 53:55technology and iPhone apps.
• 53:56I think a lot of these aren't
• 53:59really validated and I don't think
• 54:01anything beats right now seeing a
• 54:04dermatologist for any evaluation,
• 54:06maybe 1. Technology,
• 54:09we'll get there.
• 54:11So immunotherapy first, technology second.
• 54:14So we do have a couple of
• 54:16questions that have come in.
• 54:17So Shepherd, Stone has or Stone Shepherd
• 54:21I'm not sure has asked when should a
• 54:24PCP perform biopsy and when they when
• 54:26should they refer to a dermatologist.
• 54:28Now not all of our Pcp's do biopsy,
• 54:30but if it's within the skill set what,
• 54:33what do you think
• 54:36so? I'm aware that you know,
• 54:38primary care physicians,
• 54:39certainly you know some do biopsy.
• 54:41I think if you're going to
• 54:43biopsy a pigmented lesion,
• 54:44it's really important to to be sure
• 54:47that that you sample the lesion
• 54:49in its entirety because if you
• 54:51only sample a small portion of it,
• 54:54you might miss the Melanoma.
• 54:56Further, if it is a Melanoma
• 54:58but you transect it,
• 54:59you really won't have an accurate
• 55:02stage of the true Breslow depth.
• 55:05I would say if it's something that
• 55:07you've been trained in and and
• 55:08you're capable of doing do so.
• 55:10But in general,
• 55:11you know this is kind of what bread
• 55:13and butter dermatology is and we're
• 55:14very happy to see those patients.
• 55:18And another question from Dr.
• 55:21Allard, what are your Melanoma
• 55:24screening recommendations by age
• 55:26despite the USPTF not recommending
• 55:29annual screening? Another
• 55:31really good question.
• 55:31I think a lot of it comes to those
• 55:34risk factors that I alluded to.
• 55:36I don't think somebody who has few
• 55:39nevi darker skin, no personal or
• 55:41family history needs to to be screened.
• 55:44If you see someone even at a young
• 55:47age who has a strong family history,
• 55:50has a lot of nevi and in
• 55:53particular has a lesion of concern,
• 55:55I think that's the key.
• 55:56If there's a lesion of concern,
• 55:58that's an automatic should be evaluated.
• 56:00Those screening guidelines don't
• 56:02apply to a concerning lesion.
• 56:04I think if it's a young child
• 56:06who maybe has a parent or grant,
• 56:08you know, with Melanoma but
• 56:09certainly is a primary care doctor,
• 56:11you don't see anything concerning.
• 56:13I don't think it's urgent to
• 56:15have that that child screened
• 56:21well. That's the end of our questions that
• 56:25have come in and also the end of our hour.
• 56:29So again, I, you know,
• 56:30each of you spent time to prepare for this.
• 56:33It was just so well delivered and full
• 56:36of information that I think is really,
• 56:38really helpful. So these connections,
• 56:41these moments are valuable
• 56:44and and I thank you for that.
• 56:45And I thank you to those who took time
• 56:47to listen despite a like very bad,
• 56:50awful, horrible IT day here at the
• 56:53health system because we know it
• 56:56took special effort to get here.
• 56:58And encourage your friends to watch the
• 57:00recording, which we'll also send out.
• 57:01Good. Thank you all.