Smilow Shares: Kidney Cancer

April 01, 2022

Information

March 31, 2022

Presentations by: Harriet Kluger, MD | Patrick A. Kenney, MD | David A. Braun, MD, PhD | Michael Hurwitz, PhD, MD | Claire Healy, CGC

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To CiteDCA Citation Guide

00:00Sugar I'm a professor of
00:02medicine in medical oncology.
00:04I see patients with kidney and
00:06skin cancers wanna thank you all
00:08for joining us tonight we have
00:10a wonderful panel of speakers.
00:12You're going to talk to us specifically.
00:13Bad kidney cancer. We
00:17will have 4 presentations total
00:20and after that there'll be some
00:21time for questions and answers.
00:23If you have any questions feel free
00:25to put them in the chat and we will.
00:28We will try to answer them at the end of
00:31each session to the best of our ability.
00:34So we have four of the four speakers.
00:38I'm going to start introducing by
00:39introducing the first speaker.
00:41It's doctor Patrick Kenny.
00:42He is one of our urologic surgeons
00:45and he's going to talk to us about
00:47surgical approaches to kidney cancer.
00:49So Pat take it away.
00:54Thank you so much Mary.
00:55It's a pleasure to be here with everybody
00:57and as Doctor Krueger mentioned,
01:00I think we'll be taking some questions
01:03at the end and as a surgeon.
01:05I have the pleasure of helping take
01:09care of patients throughout a variety.
01:13Of different parts of their cancer journey,
01:16but also throughout a variety of
01:18different kind of kidney cancer problems.
01:21So I think it'd be really helpful to kind
01:24of first talk about some patient resources,
01:26but then also to review a little bit
01:29just about kind of kidney cancer.
01:31101 and we'll talk about we
01:33call localized kidney cancers.
01:35That's kidney cancer.
01:36That's in in the kidney itself,
01:38as well as the role for surgery.
01:41To kind of more advanced or
01:43higher risk cancers.
01:48So some patient resources
01:49I think are excellent.
01:50There's a group called the
01:52Kidney Cancer Association.
01:53If you're not familiar,
01:54it's a really fantastic
01:56organization. The URL is
01:59www.kidneycancer.org.
02:00They have fantastic patient resources,
02:03very good pamphlets, information, blogs.
02:07There's some great videos as well
02:09as the ability to to really kind
02:12of getting in touch and be part
02:14of the kidney cancer community.
02:16The Urology Care Foundation also
02:18has some excellent resources at
02:21urologyhealth.org, in particular,
02:22this kidney cancer patient guide,
02:24I think is a very good and brief review,
02:28so I do have some kind of this is a
02:31a picture of a of a biopsy specimen
02:33of a benign tumor of the kidney,
02:36and I think one of the most important
02:38things for patients to know is that
02:39if you're diagnosed or if a patient
02:41is diagnosed with a mass of the
02:43kidney or a tumor of the kidney,
02:44it's not necessarily cancer.
02:47About 7% of kidney tumors or
02:50something called an oncocytoma,
02:51which is a benign tumor of the kidney.
02:54Although it's difficult to distinguish
02:55on biopsy from some kidney cancers,
02:58they're quite common and I see
02:59them a lot in my practice.
03:01They're very often treated it because on
03:03imaging they can look very much like a
03:06kidney cancer at the bottom of the screen.
03:08Here is something called an angiomyolipoma,
03:10and this is a fat containing
03:12tumor of the kidney.
03:14I highlighted it in yellow,
03:15'cause it could be a little
03:16bit difficult to see.
03:17Because it's near the the fat
03:20that's normally around the kidney,
03:22the vast majority of these are benign.
03:24They're they don't spread elsewhere,
03:26but they can bleed,
03:27so we often do treat them for that reason,
03:30but important to keep in mind that
03:32kidney tumor does not necessarily
03:35mean kidney cancer.
03:36Now the majority of the kidney
03:38tumors we see are cancer.
03:40About 90% of the malignant or
03:42cancerous tumors of the kidney,
03:44or something called renal cell carcinoma.
03:46That's a family, really.
03:48A family of kidney cancers that are
03:51all separate distinct tumors that
03:53arise from different kind of different
03:56parts of what's called the nephron.
03:58The functional unit of the kidney,
04:00about 5% of malignant kidney tumors
04:02are what's called urothelial cancer.
04:04That's the same type of cancer.
04:06That impacts the bladder.
04:07It really arises from the lining
04:09of the urinary tract,
04:10which you can see here,
04:11which is this tan kind of urine
04:14collecting system and only about 1%
04:18of malignant or cancerous tumors of
04:20the kidney or tumors that have spread
04:22to the kidney from another location.
04:24We can see it from cancer,
04:26a cancer called Melanoma or breast cancers,
04:29lung cancers,
04:30and the most common other cancer that
04:34spreads to the kidney is lymphoma.
04:36But the focus of what we're speaking
04:38about tonight really is renal cell carcinoma.
04:41That family of related tumors that
04:43arise from what's called the nephron.
04:46This represents about 4% of new
04:48kidney of new cancers in the
04:50United States last year,
04:52about 76,000 patients across the
04:54United States were diagnosed with
04:56kidney cancer and about 14,000
04:58patients died of kidney cancer
05:00last year in the United States
05:02over their lifetimes, up to 2% of the
05:05population will develop a kidney cancer.
05:07It predominantly happens as people age,
05:08so in the 6th, 7th and 8th decades of life.
05:11But we do see it in younger patients
05:13and you'll hear about that this evening
05:15that there are hereditary syndromes that
05:17can impact the risk of kidney cancer.
05:19Risk factors is a very common question.
05:22I think the most important thing to know is
05:24that if someone developed a kidney cancer,
05:26it is very rarely do to something that
05:28they did. It's more common by chance,
05:31but there is an association with
05:32things like high blood pressure,
05:33smoking, being overweight,
05:35chronic kidney disease or dialysis can
05:38increase the risk of developing a kidney
05:40cancer as well as some exposures to
05:43chemicals like chlorinated solvents.
05:45We'll again.
05:45You'll also will hear about the idea of
05:47hereditary risk, and is there a gene?
05:50Or set of genes that may have impacted
05:52the risk of developing a kidney cancer.
05:54Again, kidney cancer renal cell carcinoma
05:56really is a family of kidney tumors.
06:00The most common is something
06:01called clear cell kidney cancer.
06:03About that represents about 3/4 of cases
06:06of kidney cancer papillary kidney cancer,
06:07of which there are two types,
06:09represents about 15 to 20% of kidney
06:12tumor of kidney cancers and chromophobe.
06:15Kidney cancer represents about 7%.
06:17The remainder are much less common
06:19things like.
06:20Medullary collecting duct and translocation.
06:22Kidney cancers.
06:23The reason this is important is although
06:26these are all renal cell carcinoma,
06:28they really have a very wide spectrum of
06:31behaviors so this is really important for
06:33deciding about what type of treatment,
06:35how aggressive a treatment might
06:36be needed or the risk of a cancer
06:38spreading elsewhere.
06:39It also can impact the types of
06:42treatments we offer and how people,
06:44how people tumors respond to that treatment.
06:49We often are asked questions about how
06:52is what's the stage of my tumor and what
06:55tumor stage is really is is rather simple.
06:57It's where are the cancer cells and
07:01as as a surgeon, I often see patients
07:04with stage one or two kidney cancers,
07:07and those are tumors that are confined
07:09to the kidney and their stage one if
07:11it's 7 centimeters or less, stage two,
07:13if they're greater than 7 centimeters,
07:15a stage three kidney cancer is shown here.
07:18On the left I I think you can see my
07:21cursor and it's a tumor that might
07:23involve the fat around the kidney,
07:24not just push against the fat,
07:27but actually microscopically grow
07:28into the fat around the kidney.
07:30Or it might involve the urine
07:32collecting system, or even the blood
07:34vessels that drain the kidney,
07:35called a tumor thrombus.
07:38Or it may be a tumor that's
07:40otherwise confined to the kidney,
07:41but which has spread to lymph nodes.
07:43These little green areas here,
07:44which some of which have
07:46yellow cancer within them.
07:48A stage four kidney cancer,
07:49on the other hand, maybe in the kidney,
07:53but growing directly into an organ nearby,
07:55not spreading to it through
07:57the bloodstream necessarily.
07:58But growing into it,
07:59such as into the adrenal gland or a
08:02tumor that's confined to the kidney,
08:03but which has spread through the
08:06bloodstream to other places either.
08:08Places like the lung,
08:10liver,
08:10bones or also through the lymph
08:12nodes outside of the area near
08:14the kidney such as the lymph
08:16nodes above the diaphragm.
08:20It's important to know that
08:22at the time of diagnosis,
08:24the vast majority of patients have a
08:26tumor that's confined to the kidney.
08:28About 70% of patients, about 14%,
08:31about 14% of patients in the United
08:34States have tumors that are regional,
08:36so they either are growing outside of
08:38the kidney or into adjacent lymph nodes.
08:41The classic way that patients
08:43used to come in to see us.
08:45But this only happens at about 5% or
08:47less of the time now is with symptoms,
08:49so a mask that they could feel on their side,
08:52blood in the urine, or pain.
08:56This cancer type used to be
08:58called the internist tumor,
08:59because when it is larger
09:00or as spread elsewhere,
09:02it's very common for patients
09:03to have other symptoms and they
09:05might be difficult to diagnose.
09:06Weight loss, loss of energy, fevers even.
09:11And then blood changes in the values
09:15on their blood tests like anemia
09:17or even high red blood cell count.
09:19High calcium changes in their liver
09:22function tests in the modern era,
09:24though most patients don't have any
09:26symptoms and these are discovered
09:28incidentally.
09:29This instant idea of incidental diagnosis,
09:31I think, is a really important one.
09:33It brings up this idea of what's
09:35called over diagnosis.
09:36This is a chart that shows that
09:38over the past few decades,
09:40more and more people in the United
09:43States are being exposed to CT scans,
09:46and so we have more and more opportunity
09:49to find incidental tumors that might
09:51otherwise not cause patients or problem.
09:54And so the concept of overdiagnosis
09:58is when the diagnosis of a tumor
10:01is increasing and throughout the
10:0390s and early 2000s.
10:04It seemed like there was an epidemic
10:06of new kidney cancer being diagnosed,
10:08but at the same time the number
10:10of patients who were dying from
10:12kidney cancer did not change.
10:13And So what this means is that we
10:15were diagnosing tumors that were
10:17not going to be harming patients,
10:18and so this is overdiagnosis.
10:21This is a really interesting study that
10:23the map of the United States here shows.
10:26Variation from different regions
10:27in the use of CAT scans and so
10:31over a five year period of time,
10:33more than 40% of patients across
10:35the United States who have Medicare
10:37had a CAT scan of their chest or
10:39cat scan of their abdomen and this
10:41varied by regions as low as 30%
10:43in one area of California,
10:45higher than 50% in Sun City, AZ.
10:47And really interestingly,
10:49the more frequently cat scans
10:51were happening in an area,
10:53the more frequently patients
10:54were having an affair.
10:55Ectomy meaning their kidneys.
10:57Removed and so if you if a patient
10:59lives in a high scanning region,
11:01they're actually at higher
11:02risk of losing a kidney and the
11:05risks associated with that.
11:07So this brings up something really important.
11:08How do we decide and how to treat
11:11a patient who has a kidney tumor
11:13and what I would argue is that
11:15for small kidney mass is one of
11:17the first things we should think
11:18about. Is something called active
11:20surveillance, and this is the
11:22idea where we need to uncouple the
11:24idea of diagnosing that tumor,
11:25the one that's incidental on a cat scan
11:27from the treatment of that kidney tumor,
11:30we know that 20 to 30% of those
11:32small masses are benign, like those
11:33tumors I mentioned at the beginning.
11:35And if they're cancer, they're commonly.
11:37It's called indolent, not aggressive.
11:41This is an ideal approach for masses
11:43that are less than 3 centimeters in size
11:45or even up to 4 centimeters that are
11:48low stage and what we do is we image
11:50every six months and we look to see if
11:52it's growing faster than we'd like,
11:54so more than 5 millimeters a year,
11:56or if it's going to be above 3 centimeters
11:58and in some patients 4 centimeters.
12:01And at that point that's when we would
12:03intervene and do a procedure to treat
12:06the tumor. So what are the outcomes?
12:08Well, with this,
12:09with ten years of follow-up in
12:11a large series of patients,
12:13there was no difference in what's
12:15called cancer specific survival,
12:16meaning being alive.
12:19And not having died of kidney
12:22cancer and so 99% in either group.
12:25Whether you had treatment upfront or
12:28whether you went on surveillance,
12:29there was 99 greater than 99% cancer
12:32specific survival at 10 years.
12:34And importantly,
12:352/3 of patients didn't meet a trigger
12:37for coming off of surveillance,
12:39so it didn't really either either
12:42didn't grow or grow slowly,
12:44and also really,
12:45importantly,
12:45half of the patients in that this
12:47group who came off surveillance came
12:49off surveillance 'cause they chose to.
12:51And so had treatment for for
12:53their preference,
12:54really important to know that
12:55active surveillance is an option.
12:57It's a safe option and the risk of
13:01spread in published active surveillance
13:03series ranges from from up to 2%.
13:06But it's really important to know
13:08that's only been in mass is greater
13:10than 3 centimeters that are growing,
13:11so it's a very,
13:12very safe option for mass is
13:14less than 3 centimeters,
13:15particularly if they're growing
13:16at a slow rate or not at all.
13:20Maslow said something in the 1960s.
13:23I suppose it's tempting if the
13:24only tool you have is a hammer to
13:27treat everything as if it's a nail,
13:28and so as a surgeon it can be really
13:30tempting to treat every patient
13:32with a small renal mass with surgery
13:34and it's just not the right thing.
13:35Sometimes doing nothing can
13:37be very difficult for.
13:38For patients can also be very difficult
13:41to not intervene on something.
13:43But this is a very innovative,
13:45very innovative approach.
13:46That's an important one for all
13:48of us to recognize that sometimes
13:50doing nothing is the right approach.
13:53Kidney mass biopsy.
13:54This is a question that comes up a lot.
13:56It used to not really be done
13:59unless we suspected lymphoma cancer.
14:01Having spread to the kidney or infection,
14:03but because kidney mass biopsy in
14:05the modern era is so much better
14:07with a low rate of complications,
14:09very little risk or no risk really
14:12of tumor seeding. And high accuracy.
14:14Kidney mass biopsy can be really
14:17helpful so it has what's called
14:19a positive predictive value of
14:21greater than 99%,
14:22meaning that if it diagnosis a kidney cancer,
14:25we can trust that diagnosis.
14:27The non diagnostic rate is
14:29about 10% up to 14%,
14:31but if we do a repeat biopsy
14:35that that increases the the rate
14:38of diagnosis substantially.
14:40Really importantly,
14:41is there are limitations of biopsy.
14:43The kidney tumors can be heterogeneous,
14:45so not all areas of kidney tumors
14:47are the same,
14:48and biopsy isn't perfect for grade.
14:50If it's an aggressive cancer or not.
14:53So there we shouldn't always do
14:55a kidney mass biopsy,
14:57but there are really important
14:58times where it's a great tool.
15:00This is what it looks like
15:01where a patient has a CAT scan.
15:03This white line is a needle that's
15:05entering the kidney,
15:06the kidney mass.
15:07This shows a needle entering
15:10the mass and then and taking
15:12out a small sample of tissue.
15:16So the idea of when to obtain a biopsy.
15:19It's sometimes it really is.
15:21Sometimes, as one of my colleagues said,
15:23more than never, but less than always,
15:25and so we do it.
15:26If we suspect lymphoma, Abscess,
15:30or spread to the kid spread of
15:32another cancer to the kidney.
15:34If the patient is.
15:38If the patients candidate
15:39for active surveillance,
15:41depending on a biopsy result,
15:42we might do a biopsy.
15:44If we're planning on doing an
15:46ablation and not removing the tumor,
15:47that's the time to do a biopsy,
15:49so we can define what it is,
15:51and if the patient end the the treatment
15:53team are willing to observe a tumor.
15:56Depending on the biopsy result,
15:58a biopsy can be really,
15:59really helpful.
16:01It's not just biopsy,
16:02though that can help us decide whether
16:04a mass is safe for surveillance.
16:05There is an imaging study
16:08called a SESTAMIBI scan,
16:09and this is used typically for something
16:11else other than kidney tumors.
16:13But over the past five years or so
16:15it's it's got an increasing use.
16:18You can see at the top.
16:19This is what's called an
16:20uncle Cytoma benign tumor,
16:22and on a sestamibi that
16:24oncocytoma lights up bright.
16:27This is a kidney tumor
16:28down here at the bottom,
16:29a kidney cancer down at the bottom.
16:31You can see it's what we call cold.
16:32It does not take up the sestamibi.
16:35Basically the kidney cancers have a
16:37little pump in them that pumps the
16:39sestamibi out and the oncocytoma's
16:41have have are packed with something
16:43called mitochondria that take
16:44up the sestamibi and they don't
16:46have the pumps to get rid of it,
16:48so that's why it's so hot.
16:50It's a very active area of investigation.
16:52We are using this here to help our
16:54patients decide on treatment for
16:56small kidney masses. It is a good.
16:58It seems to be a good adjunct to biopsy,
17:00but it is still an area of investigation.
17:03So how do we treat localized kidney cancer?
17:05I ask my patients to think about
17:083 areas to consider.
17:09Three things cancer control
17:11if that's important.
17:12If that's necessary,
17:14sparing kidney function and then
17:16risks recovery and quality of life.
17:18So what is the evolution
17:19of kidney cancer surgery?
17:21What does it look like from the 50s,
17:22sixties, 70s and 80s?
17:24We really did radical nephric to me,
17:26and so this is removal of the whole kidney,
17:28including lymph nodes
17:29including the adrenal gland,
17:31all the fat around the kidney,
17:33radical meaning.
17:33From the word meaning roots
17:35right to take the cancer up by
17:38its roots and we only did what's
17:40called partial nephrectomy.
17:40Me just removing the mass in
17:42a thin rim of normal tissue.
17:43Only in very select cases,
17:46such as if the patient only had one
17:48kidney starting in the 90s and the
17:502000s we realized that we were able
17:52to not take out the adrenal gland
17:54because imaging had improved so much.
17:56If the adrenal looks normal,
17:58we don't take it out.
17:58Same thing for lymph nodes.
18:00We don't take them out unless
18:01they're abnormal and then we started
18:03to do what's called elective.
18:04Partial nephrectomy so doing a
18:06partial nephrectomy in patients
18:07who have two kidneys.
18:10From 2010, kind of beyond,
18:13we've done increasingly complex,
18:14minimally invasive surgery,
18:16including use of the surgical robot.
18:18A big advance has been in something called
18:21Irraz enhanced recovery after surgery,
18:23where we're getting patients home and
18:25back to their usual lives faster.
18:28A lot of focus on preventing the
18:30complications of surgery such as blood
18:32clot and surgical site infections.
18:33I think most importantly,
18:35integrating surgery with
18:36medications to treat the cancer.
18:38Why is this important?
18:40Well, surgical advances really
18:42have focused on risks recovery,
18:44quality of life,
18:45sparing kidney function,
18:46and by doing that we've really done
18:48less so doing surveillance doing
18:49partial nephric to me, doing ablation.
18:52Doing minimally invasive surgery but
18:55surgical advances have not really done
18:58much from a cancer control perspective.
19:00What's done that really
19:02is doing more meaning,
19:03not just surgery but integrating
19:06surgery with other treatment
19:08modalities such as medication.
19:10I'd like to quickly go through some of
19:12the treatment options one is ablation.
19:14This is freezing or frying the mass.
19:16Most commonly here we do what's called
19:18percutaneous or through the skin,
19:19cryo ablation.
19:20It's done by the interventional radiologist.
19:23It's a great option for mass,
19:24is less than 3 centimeters in
19:26size to very low risk procedure.
19:28Very well tolerated people go
19:29home the same day no incision.
19:33It has its pairs kidney function
19:35similar to partial nephrectomy.
19:37Me, that's great.
19:38It does have a slightly higher risk of
19:41cancer recurrence than surgery does,
19:43but the good news is a second ablation takes
19:46care of of the vast majority of those,
19:48so it's a very very good option if patients
19:51are not great surgical candidates,
19:53or in a very small,
19:54very accessible tumor in a patient who
19:56doesn't feel comfortable with surveillance.
19:58The key thing is location.
20:00This is an ideally situated tumor
20:01for ablation far away from the
20:03blood vessels in the kidney.
20:05But if there there can be tumors
20:06that are close to the blood vessels
20:08close to the urine collecting system
20:09where ablation is not a good option.
20:13This is just what ablation looks like.
20:15This is a tumor at the
20:16top of the left kidney.
20:18A biopsy was done, then an ultrasound,
20:20then a cryotherapy probe was put in here.
20:24The patient did have a
20:25little bit of bleeding.
20:26You can see after the procedure which is OK.
20:29They then had a small recurrence.
20:31They cut off the blood flow
20:33to that portion of the kidney.
20:34Then it was frozen.
20:35This is from a research paper,
20:36not from our center.
20:38It was frozen again and then four
20:40years later no sign of of any cancer.
20:42It's a lot to go through,
20:43but the patient did not need surgery.
20:47Partial diff ectomy like ablation,
20:50spares kidney,
20:50but it's surgery and in that
20:53surgery we remove the tumor suture.
20:55The rest of the kidney back together.
20:57This can be done open laparoscopic
20:59Lee or much more commonly
21:01now it's done robotically.
21:02We prioritize partial nephric to me even
21:05when the tumors are highly highly complex.
21:08If a patient has only one kidney,
21:10if there's tumors in both kidneys or
21:12if they have chronic kidney disease.
21:15We know from retrospective research
21:17looking back at the patients we've
21:19treated that partial effectively
21:20reduces the risk of chronic kidney
21:22disease compared to removing the whole
21:24thing compared to radical nephrectomy,
21:26and it provides the exact
21:28same cancer control.
21:29This is a really,
21:31really important option for our
21:33patients and is very commonly employed,
21:35so partial direct to me these days is
21:38still done at many centers open they
21:41with an open incision, and that's OK.
21:44The key?
21:45The advantage of minimally
21:46invasive surgery though,
21:47is a really significant
21:49improvement in patients recovery,
21:51even for highly complicated
21:53tumors like you see down here,
21:54we do the vast majority of our partial
21:56infectees with robotic surgery. Here I am.
21:59I am a really big fan of the surgical robot.
22:05It's made by a company called
22:06Intuitive Surgical.
22:07It's pictured here.
22:08This is the console where the surgeon sits.
22:10It has a dual eyepiece
22:12that provides a 3D view.
22:14This is the robot itself that has.
22:16Four different minimally invasive
22:19instruments that that we use.
22:22To do the operation itself,
22:23and this is what's called the vision cart,
22:25where my assistant who's at the
22:26bedside is able to also see what's
22:29happening inside the abdomen.
22:30This is the eyepiece I look through.
22:32There's a.
22:33These are the handpieces that control
22:35whole variety of instruments,
22:36including a 3D camera and a variety
22:39of other instruments for suturing,
22:41and for cauterizing and
22:44otherwise treating tissue.
22:46Radical nephrectomy,
22:47unlike partial nephric to me,
22:49is we remove the entire kidney.
22:50We remove the fat around it, we remove.
22:52In some cases, the adrenal gland,
22:54and, in some cases,
22:55cases lymph nodes and the factors that
22:58make us remove the entire kidney is if
23:01a partial fraction be just not feasible,
23:04it's the radical nephrectomy
23:05is the standard approach for
23:07what's called a T1B tumor,
23:08or higher.
23:09If the tumor is just highly
23:11complicated, if it's locally advanced,
23:13if it's involving the vein or lymph nodes,
23:15a standard approach is to remove the whole.
23:17The whole kidney in general.
23:19There are fewer complications
23:20with radical and effectively
23:21than with partial nephrectomy.
23:22Me, but obviously with losing the
23:25whole kidney there is increased risk
23:27of developing chronic kidney disease.
23:30There is a time where we almost
23:31always do surgery these days.
23:33Still with open surgery, and that's if
23:35the kidney tumor invades a blood vessel,
23:38and so kidney tumors can invade a big vein
23:40in the belly called inferior vena cava,
23:43and that can even extend all
23:44the way up into the heart and.
23:46In those cases,
23:48we have a team here of liver surgeons,
23:51heart surgeons,
23:52and neurologists who treat those
23:54patients primarily with open
23:56surgery to remove the kidney and to
23:58remove the entire tumor thrombus.
24:03Kidney surgery for many patients,
24:05though, may not be enough in some.
24:08Obviously it's not necessary,
24:09in others it may not be enough,
24:10and so we've investigated
24:11what we call adjuvant therapy,
24:13and this is medications after surgery.
24:17To reduce the risk of the cancer coming back,
24:20there have been dozens of trials done in
24:22kidney cancer dating back more than 50 years.
24:24All of them were negative until recently
24:26there was a medication that has an FDA
24:28approval for in the agement setting.
24:30It's used by some medical oncologists.
24:32It's generally not used here, though,
24:34and this is a medication called sunitinib.
24:36It tends to cause a fair amount of
24:38complications and what you can see here is
24:40this is what's called the overall survival.
24:43Survival curves.
24:44There's actually 2 lines there overlapping,
24:46and that drug does not seem.
24:48To help patients live longer,
24:50we generally don't use it.
24:51There's a very promising study.
24:55Called keynote 564 studying a what's called
24:58an immune checkpoint drug or pembrook.
25:01It's a pembrolizumab or Pembroke
25:03and this showed a significant
25:04improvement in what's called disease.
25:06Free survival and some promising.
25:11Promising appearing curve for
25:13what's called overall survival
25:14or helping patients live longer.
25:16It is FDA authorized and we're
25:18still at this point,
25:19I think,
25:20very much as a whole field trying
25:21to sort out which patients are the
25:23appropriate patients for this drug.
25:25And we're all anxiously awaiting
25:27the overall survival data.
25:29I think the summary here is that
25:31not all kidney cancer is the same.
25:32It's important to know that typed the size,
25:34the stage, the location.
25:36It's important to decide on
25:37treatment if it's necessary,
25:39and if it if treatment is necessary.
25:41Which is the best one we should
25:42do less when we safely can and
25:44use a team approach to the most
25:46challenging cases and very clearly
25:48integrating surgery and medication
25:50therapy is really a key frontier
25:52for us over the next decade.
25:54Thank you very much for your time.
25:56Thank you so much,
25:57doctor Kenny, that was great.
25:59I earned. I learned a lot.
26:02There are some questions in the chat
26:03that have been answered and some
26:05that happen, so if OK with you,
26:07I'd just like to ask you those
26:08that have not been answered yet.
26:12So there's a question about how
26:14often do you see a diagnosis
26:17of metastatic kidney cancer
26:18without a clear primary tumor?
26:22That's a, that's a great question.
26:24We we really don't at that happens
26:26a lot in other tumor types,
26:27but most often in kidney cancer there's a.
26:31There's an obvious primary tumor.
26:32I myself have not taken care of
26:34a patient who's had metastatic
26:36kidney cancer without a primary.
26:38I'm not sure Harriet or
26:39Michael or David if you have.
26:42Yeah, I've seen it once.
26:44Yeah, we have it.
26:45It happens a little, you know.
26:46Uncommonly, I I think the question let me.
26:48Maybe I'll answer this a little bit.
26:50You know there's sort of a few different
26:52possibilities every once in a long,
26:53long, long while,
26:54even though there's a tumor there,
26:56you can't exactly see it because
26:57it's about the same density on
26:59the scans as the other tissue.
27:01So there's really something there,
27:02but no one really detected it.
27:03And then the other thing that we know
27:05that happens sometimes in kidney
27:07cancer is that there's a tumor there
27:09that get then sort of went away,
27:10even though other tumors have remained.
27:13And I think all of us who treat
27:15metastatic cancer have seen that.
27:17That happens and not that many cancers,
27:19but it does sometimes happen
27:20in kidney and Melanoma.
27:21Actually, which Doctor Cooper treats that?
27:23You'll see a tumor start and then go away.
27:25So maybe the tumor was there,
27:27then something spread and then it went away.
27:31There's something called the abscopal
27:32effect or the Lazarus effect,
27:34where it happens we see it in kidney cancer,
27:38especially if there's been a few reports
27:40of patients who have had a metastasis
27:42treated either with ablation or radiation,
27:44and then the primary tumor or metastasis
27:47and other sites have melted away.
27:49It happens in kidney cancer, but quite rare.
27:53So there was
27:54a question about whether papillary
27:55renal cell carcinoma is the same
27:57as papillary thyroid and actually
27:59Doctor Brown who's got the orange
28:00tie for kidney cancer, answered it,
28:02but I don't know that everybody
28:03saw that and the answer is no,
28:05it's not. It just looks the
28:07same under them. It has similar
28:08features in the under the microscope
28:10that the cell of origin of origin
28:12is quite different.
28:15Then Patrick there was a question about
28:17how often you have clear cell renal
28:20cell carcinoma that has both sarcomatoid
28:23and rhabdoid features.
28:26So Sarcomatoid and Rhabdoid
28:28features themselves are
28:29relatively rare in combination.
28:32We do see it, but also relatively rare.
28:35They are higher grade features of a
28:39kidney tumor that tends to mean the
28:42tumor itself is more aggressive and
28:45also may impact our treatment selection.
28:48For instance, if a patient
28:50has metastatic kidney cancer,
28:52sometimes surgery itself can can be
28:55appropriate as a first treatment.
28:57Option and if we know that a
28:59patient has a sarcomatoid kidney
29:01cancer or a rhabdoid kidney cancer
29:03that has spread elsewhere.
29:05Oftentimes,
29:06surgery may not be the right
29:07first approach for those patients,
29:09and where medication may be
29:12the first right approach.
29:13And in the case where the medication has
29:16done a good job of stabilizing the tumor
29:18or the tumor has responded to the medication,
29:21surgery,
29:21then might be an option.
29:23But but Sarcomatoid and Rhabdoid
29:26together relatively.
29:27Rare I I don't have a good sense
29:30of whether that would change
29:33a patient's prognosis.
29:34They're all still grade 4.
29:38Then there's a question about
29:40you. You made a comment about kidney
29:42disease, and I think sometimes
29:43as physicians we use terminology.
29:45That's not not all that clear.
29:48So there was a request for
29:50clarification about kidney disease
29:51versus kidney cancer.
29:54Great question.
29:55Thank you for pointing that out.
29:56I I have to I have to say I I
29:58I do tend to slip into medical
30:00words and I I'm sorry I so kidney
30:02disease has to do with the ability
30:04of the kidneys to fill the to
30:06perform their job of filtration.
30:08So we have various different
30:10ways of measuring that.
30:11One of them is a blood test
30:13called serum creatinine,
30:14and when the creatinine is elevated
30:16that indicates a reduction in
30:17kidney function and we call that
30:19chronic kidney disease, or CKD,
30:21and that's when it's persistent over the
30:25course of weeks or months or longer.
30:28Like one of the key things
30:30about partial nephrectomy,
30:31me active surveillance ablation
30:33compared to radical nephrectomy is that
30:36for patients who have kidney disease
30:37or who are trying to prevent it,
30:40those what we call nephron sparing
30:42or kidney sparing approaches may
30:44be a better option because they're
30:46associated with a lower risk of
30:48developing kidney dysfunction.
30:50Thank you for that,
30:51that was a great answer.
30:53Then there's a question
30:55about stage three cancer.
30:57There's a comment.
30:58From somebody who had a 4.6
31:00centimeter tumor,
31:01but it was called stage three.
31:03Can you clarify that
31:05how that's possible?
31:08So so a 4.6 centimeter tumor that can be
31:14stage three really kind of for two reasons.
31:17One would be if it there was a the
31:20tumor had associated in lymph nodes.
31:22So meaning if there was
31:24involvement of the lymph nodes,
31:26then no matter what the the,
31:28the tumor size or or T stage is,
31:31it would be a stage 3 tumor.
31:33Or if that tumor was involving
31:35the fat around the kidney or
31:37in the center of the kidney.
31:39The urine collecting system or a blood
31:42vessel within the kidney and that would
31:44be stage 3 even for very small tumors,
31:47and so I've taken care of
31:49patients who've had very, very,
31:50very small tumors that were stage
31:53three just based on involvement
31:55of those other features.
31:58Then are there instances where somebody
32:00has metastatic kidney cancer and
32:02there's no surgery done?
32:05Very, very commonly.
32:06So you the paradigm starting about
32:0920 years ago, was to do something
32:12called cytoreductive nephrectomy.
32:13So they're mean to remove the kidney when
32:16in the setting of kidney cancer spread,
32:18and for a variety of reasons
32:20we do that less commonly now.
32:22It's very, very nuanced,
32:24but there was an important study
32:27a few years ago called Carmina,
32:28and it was a study looking at
32:30use of a medication alone or
32:33a medication plus surgery,
32:34and it showed that that medication alone.
32:36Performed just as well as surgery,
32:38plus the medication so very commonly
32:40these days we take care of patients with
32:44kidney cancer that spread elsewhere
32:45and they don't have to have surgery.
32:48Thank you, director
32:50Kitty. Thank you so much for
32:52a wonderful presentation.
32:53And now I've got the distinct pleasure
32:56of introducing our second speaker.
32:58It's doctor Michael Hurwitz,
33:00who is one of my fellow oncologists Mike.
33:04Yeah, so I share screen here.
33:05See if I can get the store.
33:10Is it visible? Yes, we've got
33:13your slide sorter hold on.
33:15Let me go to the beginning again.
33:20Oh wait a minute. Sorry folks.
33:25Why isn't it going to?
33:28Now can everybody spit?
33:30Yep. OK alright great so.
33:33Hi everyone, welcome again.
33:35As Harriet said, I'm I'm I'm one of
33:37the medical oncologists tonight.
33:38I treat kidney cancers and also
33:41bladder and prostate cancers.
33:43And I'm going to talk about
33:45treatment of metastatic cancer.
33:46You know, I,
33:47I know that the topic here is supposed
33:49to be kidney cancer and all the
33:51various treatments that we give,
33:52but to some degree I wanted to
33:55backtrack a little bit and the reason
33:57for that is that not everybody knows
34:00some of these basics about cancer.
34:01And when I say not everybody,
34:04I mean a lot of doctors who
34:06are not kidney or cancer.
34:07Doctors aren't exactly aware of a lot of
34:10the basics of cancer in it, and the reason?
34:13That I wanna.
34:15Talk about it this way is that I
34:17think to understand how we decide to
34:20treat metastatic cancer in the kidney,
34:22it makes sense to think about
34:24sort of what cancer really is.
34:26OK, so let's start with what is cancer?
34:28Something really basic and so cancer is
34:30made up of cells that don't behave normally.
34:33And what I mean by that is that
34:34cancer is really a disease of cells.
34:37It's a disease of individual cells that
34:38are doing what they should not be doing,
34:40and they they're really three specific
34:43things that they do that that.
34:45Are the hallmarks of cancers so number
34:49one they conceded to divide even
34:51when they are not told to divide?
34:53OK two,
34:55they even continue to divide when
34:57they are told not to divide,
34:59so one is they can do divide
35:01on their own and other is when
35:02they're told to stop dividing.
35:03They continue to divide.
35:05And lastly they won't die
35:06when they're supposed to.
35:08Now some of this may not
35:09make sense to everyone here,
35:10but I think it's worth pointing
35:12out that all cells in the human
35:14body are are really in continuous
35:16conversation with each other.
35:17Cells talk to each other in various ways.
35:19I'm going to go into that a little bit
35:21and they're always sending signals to
35:23each other to say things like don't divide,
35:26do, divide,
35:27make something like make insulin for example,
35:31and they're also told the die.
35:33Sometimes a lot of cells are
35:34dying on purpose all the time.
35:36That is the way the society
35:38in your body works,
35:39so.
35:40Cancer is a disease where the cells
35:43have lost the ability to communicate,
35:45and they're dividing when they shouldn't.
35:48And you know the vast majority of of
35:51cells also that that form cancers in
35:53adults form the lining of tissues.
35:55Doctor Kenny actually referred to this
35:57before, and a lot of the linings.
35:59I don't know if everyone can see my cursor.
36:00Is that just me or can people see it?
36:03Pat, you're the only one who I can.
36:04I don't know if you're, but yeah,
36:05we can see well oh,
36:06good, good, OK, alright so so normally we
36:08have these things called called it doesn't
36:10matter the linings of tissues and obvious
36:12and often these cells are neatly on them.
36:15And I show a cell wasn't called a nucleus,
36:16middle of the cell. And then there's this
36:18process that happens when can't when,
36:20when when normal cells turn into cancers?
36:22And I also do this grayish junk here
36:24and that's that's called the there's a
36:27there's something called a submucosa,
36:29or there's something called ground substance,
36:31and that's what these cells are sitting on.
36:33OK, and that's a normal
36:35thing in in most tissues.
36:37So the first thing that can happen is the
36:38cells can divide inappropriately and then
36:40you get a lot of cells, but they're not.
36:42They don't look wrong,
36:43they're not doing anything all that abnormal.
36:45Then you have a precancerous stage,
36:47so sometimes we call these
36:48things adenoma or breast cancer.
36:50We often call it DCIS or LCIS,
36:53and then this is when the
36:55cells start looking funny,
36:56but they haven't done anything
36:59definitively cancerous yet.
37:01We call it cancer when they have
37:04actually invaded into a tissue.
37:05OK, and invasion means breaking
37:08out of this underlying membrane.
37:10That is the way we define cancer,
37:12and again,
37:12the cause of it is what I said before.
37:18There we go. OK, so.
37:20I said cancer is a disease where
37:23cells misbehave and the question
37:25is why aren't they behaving and
37:28the basic answer is that there
37:30is something called DNA mutation.
37:32So DNA is the is the blueprint for
37:36everything that is done by a solid body.
37:38So everything that is done in your
37:40body is done based on a code and that
37:43blueprint that encodes it is made up of
37:46DNA which the string of actually code.
37:49I've drawn it here. Everyones got 2.
37:51Of the same piece of code in their body.
37:55So we have we have we have paired
37:56what are called chromosomes.
37:57I only drew 2 here.
37:58We actually have 23 pairs but but either way,
38:03when a cell starts,
38:04it's maybe there's a mutation in it.
38:06OK, and I've drawn it as an X.
38:07Alright,
38:08what distinguishes cancer from other?
38:11Disease in the body is that
38:14cancer cannot control.
38:15Cancer cells are very bad at
38:19fixing DNA mutations.
38:21Normally.
38:21If you have a DNA mutation,
38:23either it will be fixed or the cell
38:24will say you know I can't fix it.
38:26The cell will kill itself.
38:27That doesn't happen with cancer
38:28and this leads to two things.
38:30First of all,
38:31what happens is more mutations
38:33develop as the cells divide OK,
38:35the second thing that happens is in every
38:39cell division you're going to get different.
38:41Cells right?
38:42Because mutations are
38:43developing all the time,
38:45but the same mutation that happens
38:47in this cell isn't necessarily
38:48going to happen in this cell.
38:50So every time there's division,
38:51you can get more and more mutations.
38:54Is this healthy?
38:55No, many,
38:56many of the cells and cancers will die.
38:59Cancer cells are not particularly healthy,
39:01but some of them will develop what
39:03we call malignant clones and they
39:05will go on to form these cancers
39:07that are very hard to control
39:08because the blueprint is wrong.
39:11They're no longer doing what
39:12they're supposed to be doing.
39:14And the last thing I want to talk
39:15about is sort of what is cancer?
39:17Is something called metastasis.
39:18I know we've all heard the term
39:21metastasis means when there is
39:22spread of a of a cancer from
39:24one area to another area and
39:26it means it's not continuous,
39:28meaning it's not the whole
39:30tumor mass growing.
39:31It's actually a cell breaking off
39:33and going somewhere else in the body.
39:35OK, so first,
39:36it's worth pointing out if everyone
39:37doesn't know this and there's
39:39no reason you would know this,
39:40that many cells in the body are able to move.
39:43They can migrate and that is
39:45what happens in cancer,
39:46so that's what's required for
39:48metastasis once they move somewhere,
39:49they have to find a place that
39:51can support their growth.
39:53OK, and there's this idea of a
39:54seal seed and soil hypothesis,
39:56for example,
39:57kidney cancers often go to bones.
39:58They often go to lung,
40:00sometimes they go to liver,
40:01other cancers don't go to those places,
40:03and that's because in addition to
40:05the fact there's the blood supply
40:08that sends it to certain places,
40:10they can only go and land in
40:12certain places and grow there. OK.
40:15And then lastly, once they do get there,
40:17they have to be able to set up a food supply,
40:19which really means the blood
40:21supply and that we have a term
40:23for that which is angiogenesis.
40:24And that's gonna be really important
40:25for how we treat kidney cancers.
40:26OK, moving on,
40:28I want to talk about how the cells
40:30actually talk to each other because
40:32I mentioned that cells talk to each
40:34other all the time and the way they
40:36talk to each other is they send things
40:38out of 1 cell and it goes to something
40:39on the other cell and the other cell
40:41has what's called a receptor to bind it.
40:43Sort of like a lock and key.
40:44So here's an example.
40:46I have the outside of the cell here,
40:48and here's the cell membrane and
40:50here's a receptor or a lock.
40:52OK, and this thing is a key,
40:54it's something called EGF.
40:55It's sent from somewhere else,
40:56and when it binds to this thing
40:59this thing turns or it changes.
41:01And actually there are things called
41:03phosphorylated groups that end up on that.
41:04Once those things are there.
41:07Something inside the cell.
41:09We'll find it.
41:11They're moving around each other
41:12all the time and it will bind to it,
41:13because this thing recognizes it,
41:16so it'll bind to it and it brings
41:19in a friend.
41:21And that friend brings in yet
41:24another thing that binds to it.
41:26And this thing called wrasses.
41:28Very important cancer.
41:29These things that I'm talking about.
41:32They're not just little things
41:33that bind to each other.
41:34They're actually little molecular machines,
41:37OK? This machine just sticks things together.
41:42OK, it's an adapter,
41:43but this is a machine that
41:46turns this machine on OK,
41:48and once this thing is on,
41:50it's a general on switch oops that
41:52turns on another protein which
41:54turns on another protein which
41:56turns on another protein and that
41:59results in cells dividing.
42:01That's actually a normal process.
42:03We want that a lot of the time
42:04you often need cells that divide.
42:06OK, you need it every day.
42:08But you don't always want it,
42:10and cancer,
42:10it's happening when it shouldn't
42:12be happening all right.
42:14So what's unique about kidney
42:15cancer that those are sort of?
42:16That's my general view of what cancer is,
42:17alright,
42:18so kidney cancer is actually
42:19as Doctor Kenny pointed out,
42:21a whole big group of cancers.
42:23Now the vast majority of of it.
42:26You know about 90% of it or more,
42:28are the types that some of which
42:30were mentioned by Doctor Kenny.
42:31Clear cell carcinoma is the most common.
42:33It's about 75% of it.
42:34There's something called papillary
42:36and chromophobe,
42:36which was mentioned before.
42:39In addition to the fact that we know there
42:41are certain types of types of cancers,
42:43there's also something called kidney cancer
42:45syndromes where they run in families,
42:47and the reason they have these cancers
42:49is because one of their genes has a
42:52DNA mutation that that results in a
42:54predisposition for these things to occur,
42:57and the one I want to talk about is
42:58something called Von Hippel, Lindau Sovon.
43:00Hippel. Lindau is a is a disease that
43:03results in tumors in many different organs,
43:07but probably the most famous one
43:09is in the kidneys.
43:11So what is von Hippel Lindau so von Hippel?
43:13Lindau is a protein that is important
43:15in something called oxygen sensing.
43:17So the cells in your body are able
43:19to actually sense when there's
43:21oxygen there and when there isn't
43:23much much oxygen there they think.
43:25Why isn't there oxygen there?
43:26Probably there's no blood supply and what
43:29happens is they send out more signals,
43:31developed blood vessels so.
43:34When there's normal oxygen.
43:37This protein, called DHL,
43:38is on what VHL does is it turns the
43:42oxygen sensing pathway off alright,
43:44so oxygen present VHL is on.
43:47Nothing happens if the pathways off
43:50nothing that the machines are all off.
43:53But when there's a low oxygen level,
43:55VHL is turned off.
43:56And then the oxygen sensing pathway
43:59is on and that results oops.
44:01In blood vessel growth in cell
44:04division and in some cell movement.
44:06In kidney cancer and people who
44:09have mutations in this VHL gene.
44:11The HL is always off 'cause it's broken.
44:14So the oxygen sensing pathway
44:16is on all the time,
44:18and so that predisposes
44:19these cancer to develop.
44:24And why is that so important?
44:26Because it turns out that we have
44:30medications that actually block parts
44:32of that oxygen sensing pathway,
44:33and actually there's a new one that I
44:35didn't put on here called bills udaff
44:37and I don't know if Doctor Brown is
44:38going to talk about that. He's nodding.
44:40He is going to talk about that.
44:42So it's we got about Bill Sudafed,
44:44but these are all medications
44:46that work similarly to turn off
44:49the oxygen sensing pathway.
44:50The other medications that we use in kidney
44:53cancer are generally things that turn
44:55on the immune system in one way or the other.
44:57And this sounds like a distinction without
44:59a difference, but is it difference?
45:01And that's how I'm going to end this
45:02by talking about the difference.
45:04Oops, one are things that actually
45:06activate the immune system and turn on,
45:08and the other type are ones that prevent
45:11the immune system from being turned off.
45:13Notably, these things are all pills,
45:16everything else is actually given by vein,
45:19and the last thing is we do not use
45:21chemotherapy and kidney cancer.
45:23It does not work there.
45:24Various theories where it doesn't work,
45:25which we can talk about,
45:26but it just doesn't work,
45:27so we don't use it.
45:29But all the other drugs,
45:30aside from the ones that are mentioned
45:32that through with oxygen sensing in DHL
45:34they have to do with the immune system.
45:36Alright,
45:36let's talk a little bit about immunity.
45:40The immune system is something
45:41that all it does.
45:42Its whole job is to distinguish
45:44the self from foreigners and then
45:45mostly to get rid of foreigners.
45:47So the way you distinguish yourself
45:49is that every cell in our body
45:52is continuously taking bits of
45:54the cell from the inside,
45:56sticking them on the surface
45:58and telling our immune system.
46:00This is part of the immune system called
46:01T cells and saying, hey, this is me.
46:04I'm part of us and T cells
46:08generally the ones that.
46:10That used to recognize this stuff.
46:12They mostly gone away because if a T
46:14cell recognizes something strongly,
46:16it tries to kill it, OK?
46:18And that's sort of how immunity works.
46:20So when you get a bacterial,
46:22let's say that invades one of your cells.
46:24The cell doesn't just show bits of itself,
46:26it also shows bits of the bacteria and
46:29that he saw may recognize that and say,
46:31oh, this is a problem.
46:32I better kill that cell because
46:34it harbors bad bacteria.
46:36Turns out that isn't enough.
46:38You need a second signal and that 2nd signal.
46:41Don't worry about the name of it,
46:43but you need a second signal.
46:44Basically cells that are invaded
46:46by bad things send out a second
46:48flag saying not only do they show
46:50you the bacteria is part of it,
46:53but they say something is going very
46:54wrong and that's recognized by the
46:56immune system, particularly T cells,
46:57and that turns them on.
46:59We call that costimulation and
47:01this is the hopefully the
47:04end point. Oh oh,
47:05there we go that's over,
47:07it kills it and that's the
47:10way the immune system works.
47:11Why am I talking about this?
47:12What does it have to do with cancer?
47:14Oh sorry, before I get to that
47:16there are two other things in
47:18addition to having that thing called
47:21costimulation that turns it on.
47:22We also have things that turn the
47:24immune system off 'cause you don't
47:25want the immune system on all the time,
47:27and one way is to block the flag.
47:31The T cell blocks that flag with
47:33this protein and with it the T
47:35cell doesn't recognize it anymore.
47:36And another way is that we have
47:38another set of thing called PD One
47:40and PDL one and that also is a
47:42signal that says turn T cells on.
47:44OK. Getting back to cancer.
47:48So as I said,
47:50we distinguish ourselves from
47:51foreigners by taking bits of us,
47:53putting them on our surfaces,
47:55and it's not recognized by the immune system.
47:58But when you have cancer.
48:00The cancer cells are abnormal and
48:03a lot of what's on their insides
48:04are abnormal and they put that on
48:06the surface and it's recognized
48:08as foreign by the T cell.
48:10So I said that those two other
48:12types of things that we used to
48:14kill cancer that we use for to treat
48:17them are both immune modulators
48:18in one way that we did,
48:19it was to turn T cells on the most.
48:23The best examples.
48:23I called interleukin 2.
48:24We still use it,
48:25but not that commonly anymore.
48:27It doesn't work that well to be honest.
48:29We can talk about that.
48:30More people have questions,
48:31but basically just activating the cell on on,
48:34on, on, on, on in.
48:36That works somewhat,
48:37but we found that works much,
48:38much,
48:39much better really.
48:40And more consistently is to stop
48:43the signals that turn T cells off,
48:46and that's what most of the
48:48medications we use nowadays are.
48:52So whoops, sorry folks.
48:56OK, so going back to our
48:57treatments and then I'm going to.
48:59Then I'm going to end.
49:01We have we can treat by blocking oxygen
49:05sensing which turns off the cell division.
49:08Probably of those cells.
49:09The cancer cells and also prevents
49:11a lot of blood vessel formation,
49:12which is important for kidney cancers.
49:14We can. Turned the immune system on,
49:17but again these are have a lot of toxicities.
49:20They don't work that well.
49:21They can only be done by specialists
49:23at very specialized centers.
49:25We do it here, but most places don't
49:27and then there's this large group.
49:28There's other group of sort of growing
49:30group of drugs that prevent the
49:32immune system from being turned off,
49:34and to be brief,
49:36we use these a lot.
49:38We use these a lot and we use them in
49:40combinations because in combinations
49:41they work better than working alone and
49:44that's what I was going to say today.
49:46Oh sorry,
49:47the last thing I was going to talk
49:49about was why don't therapies work?
49:50We've all had friends or or or even us.
49:54We have cancer therapy works
49:56and then it stops working.
49:58So one reason that things stop working
50:01is what I said before about cancers.
50:02Remember how I said that every time
50:04the cells divide you can develop
50:06new mutations in every cell that is
50:09different mutations is essentially
50:10a different is going to act
50:12differently and so at some point,
50:14even though you're controlling
50:15a lot of the growth,
50:16you're going to get growth of things that
50:18are resistant because they're different.
50:20The other thing that's really important
50:23is that cancers have the ability
50:25overtime by mutating to develop
50:27evasion from the immune system.
50:29Another reason why it's hard
50:30to treat cancers,
50:31why therapies don't work is that parks.
50:34The tumors aren't getting
50:35a blood supply very well,
50:36so they're not getting a lot of drug into.
50:38Treat them,
50:38and tumors are actually under pressure,
50:41so there it's really hard to get drug in,
50:42and that's a major reason why big tumors,
50:44especially that have a lot of what's
50:47called necrosis or cell death in them,
50:49aren't very well treated.
50:51And lastly,
50:52many of the tumors that we have
50:55tumor cells that we have a lot of.
50:56The cells are very,
50:58very slow growing.
50:59It's very hard to kill things
51:01that are slow growing for various
51:02reasons that we can talk about.
51:04With that thanks for listening.
51:06I don't know if there are any questions,
51:08but I will stop sharing.
51:12If I went way over or
51:14no, that's a wonderful overview.
51:16I think on the foundations of cancer,
51:18which is a really good thing to understand,
51:20and there's definitely comments in
51:21the chat about how that fundamental
51:22understanding is helpful for most people.
51:24Is it and are really good level as well
51:26to understand the process that's going
51:28on and then to talk about treatments?
51:31A couple questions have come up,
51:32so the first is about Opdivo
51:35therapy specifically.
51:36So immunotherapy and you hear a lot about it.
51:38And there's a just a a base question.
51:40Does it actually cure cancer?
51:43Yeah, so at Devo is one of the ones I put
51:45there so because we're sort of academic,
51:47we don't put the trade names.
51:49We only put the names of the drugs that are
51:52that that are sort of the generic names.
51:54New volume AB is up Devo and
51:57there are probably cures,
51:59especially with combinations of
52:01Opdivo and this other guy let me Mab.
52:05It's hard to say definitively, honestly,
52:07because can't kidney cancers can come back.
52:09Many, many, many years later,
52:11and we probably first started treating people
52:14with these drugs about 10-12 years ago.
52:17You know, maybe a few patients were treated
52:20a little bit before that but but but yeah,
52:22there are people who appear to
52:25be cured from that. And
52:27so another one is sort of
52:29clarification about terminology.
52:30It's someone who that is so bad.
52:33Yeah, yeah. So the question was the patient
52:34we we got cabozantinib the paperwork
52:36we received indicated chemotherapy.
52:38Is that the question that you're asking?
52:40Yeah, that was terrible on my part.
52:42I apologize so. You know, I'm.
52:45Chemotherapy is a very
52:47poorly bandied about term,
52:50so chemotherapy originally was discussed.
52:53It was described in the 1960s and it
52:55was because we have radiation therapy.
52:58We have surgical therapy, but are we
52:59going to call therapy with medicines?
53:01We'll call it chemotherapy.
53:04That and then in the 70s and 80s
53:06chemotherapy became this thing that
53:07people think about as drugs given
53:09by vein that caused nausea and
53:10hair loss and act in a certain way.
53:13You are absolutely right.
53:14All of its chemotherapy.
53:15What I was talking about,
53:17and it was not being clear.
53:18We don't use traditional chemotherapy
53:20or what we call cytotoxic chemotherapy.
53:23That is a little bit less specific,
53:26but kills abnormally growing cells.
53:29So
53:29there's a couple more questions.
53:31One is about biomarkers analogy.
53:32Talk about that a little
53:34bit in the next session.
53:35There's a couple more questions,
53:36so one that's what that come up.
53:38That's sort of more general is
53:39sort of the importance about being
53:41treated as sort of a center of
53:43excellence and academic center.
53:44That sort of sees a lot of kidney cancer.
53:46And maybe if you could speak
53:47a little bit about that,
53:48why that might be helpful in certain cases.
53:50Yeah, so so I think that the job
53:54of a general oncologist is almost
53:56impossible that there's so much to know.
53:59And not only do you have to
54:01know every single disease,
54:02but you don't have other people
54:03floating around you who do
54:05other things that are relevant.
54:06So one of the great great joys of my
54:09existence is when something that I
54:10have no idea that comes up that may
54:13have to do with localized treatment
54:14or with taking something out.
54:16I can call Pat and and and he's right
54:19there just to answer it and and so
54:21one of the things that you get from
54:23going to a center of excellence is
54:25that there are a lot of us around.
54:27We all can communicate with each other and.
54:29We have as a group.
54:31We have seen a huge amount of
54:34different things.
54:35The other thing is that because
54:37people like Doctor Braun and
54:39and and Doctor Cooper and I.
54:40Really only treat one or two diseases
54:43or my case for diseases or whatever.
54:46You see a lot of the same thing,
54:48and you've probably seen a
54:50lot more of things.
54:51Maybe sometimes we're a little more
54:53up to date because we can follow only
54:56four things rather than 100 things,
54:58but I think the best thing
54:59about the center is just the
55:01multidisciplinary features we have.
55:03Pat,
55:03we have pathologists who know
55:05a ton about the stuff who can
55:07really tell us what we're looking
55:08at under the microscope,
55:09and sometimes other people can't.
55:11Frankly,
55:11we have fantastic radiologists who
55:13are using with a lot of cancer and
55:15we have interventional radiologists
55:16who can do amazing things.
55:18And radiation oncologists who know
55:19how to deal with kidney cancer.
55:21And many don't because it's not thought
55:23to be a radiation treated disease,
55:25even though in many ways it is.
55:27That would be my answer.
55:28I'm sure everyone else has a
55:29has his own or her own answer.
55:31I couldn't agree with you more Michael.
55:33I mean, I, I think there's
55:35there's other specialties too that
55:37don't immediately come to mind.
55:40You know, we have nephrology team here,
55:43including someone who
55:44specializes in onco nephrology.
55:46So nephrology is medical doctors
55:47for the kidney for chronic.
55:49Kidney disease that we
55:50had talked about earlier,
55:51and there's someone who specializes
55:53in that in patients with cancer.
55:55That's an extraordinary resource
55:56from a surgical standpoint.
55:58I had put up a slide very
56:00briefly about tumor thrombus,
56:02or, you know,
56:03other that's when the tumor can extend even
56:06up into the heart as a General Hospital,
56:09right?
56:09We have a we have liver transplant
56:12programs and liver transplant surgeons.
56:13We have cardiac surgeons who are
56:16extraordinarily experienced,
56:17and we can call on those resources
56:19when we need to.
56:20And that's something that I think
56:22is really pretty incredible,
56:23so the advantage even just
56:26having trainees around,
56:28there's a lot of data that having
56:29trainees around helps improve outcomes.
56:31There's something really kind of
56:33magic in the water and and hopefully.
56:38That translates into better
56:39outcomes and hopefully better care.
56:42Now when you think of even this call,
56:43we have, you know, urology surgery.
56:45We have medical oncology.
56:46We have genetics.
56:47We have even this one call.
56:49Sort of a a few different specialties
56:51represented and so I think that's
56:52something unique about places like Yale
56:53and then these centers of excellence.
56:55I really, really enable that.
56:57So maybe in the interest of time we
56:59might move forward a little bit.
57:00I think there's still a couple of questions,
57:01but I think we'll hopefully have time
57:02at the end to loop back to those.
57:04Yeah David, you can answer
57:05some of those when you're done.
57:06Maybe if there are more
57:07questions for you specifically,
57:08'cause I see what they are.
57:11So you're up
57:12OK. Can you see my screen?
57:13OK? Yep, OK great.
57:16So I'm tasked with a relatively large topic,
57:19which is to talk about researching
57:21kidney cancer and really the focus
57:22of what I'm going to talk about is
57:24basic and translational research.
57:25That's often research that's
57:27done in a laboratory bench,
57:29and that's brought back to patients.
57:31So try to think about how we can
57:33better understand the disease,
57:34and most importantly,
57:34how we can better, better treat it.
57:36There's a lot to cover,
57:38so I'm going to warn you in advance.
57:40I'm going to editorialize.
57:41A fair bit of, uh,
57:42what I think I should have some of the
57:44big open questions in kidney cancer and
57:46just a little bit a little taste of it.
57:48How we are beginning to address it.
57:50And there's a huge amount
57:51of research going on.
57:52A lot that I won't be able to cover here,
57:54but hopefully my my my real hope for
57:56this sort of talk is to give you kind
57:57of a sense of the excitement in the
57:59field about how much things are changing,
58:01how much things,
58:02how many things are being studied,
58:04and how I think the future is
58:06very bright for this disease.
58:08So I think before we get started,
58:10it's helpful to take a step back
58:12and I always think to sort of
58:14know where you're going you have
58:15to sort of know where you came
58:17from and so to take a step back.
58:18Not that long ago. 20 years ago.
58:22To look at what kidney cancer
58:25treatment was like that.
58:27Like this?
58:29Sorry about that.
58:37Are you able to see the screen
58:39out right now? Yeah, perfect.
58:45I apologize, computed,
58:47decided a bad time to freeze so
58:50try one more time to restart this.
58:56My apologies.
59:06How about now?
59:07Perfect, it's perfect, OK?
59:09Third times the charm.
59:10Thank you everyone sticking with me,
59:12so I'm saying I think it's really
59:14helpful to look historically.
59:15But what kidney cancer treatment was like?
59:17You know, just 20 years ago,
59:19and so if we look at the historical data
59:21and this is largely patients treated with
59:23as doctor her which was saying things
59:26like interferon and high dose I'll two.
59:28And again we show a survival curve.
59:29This is something that doctor
59:31Kenny showed which is.
59:32Shown over time,
59:33the number of patients that are
59:35surviving at one year or 12 months,
59:37two years, three years,
59:39four years or five years,
59:40and unfortunately,
59:4120 years ago we saw this curve
59:43drop down quickly and so that we
59:45if we go to that five year mark
59:47that 60 month Mark we see you as
59:49in the single digits in terms of
59:50the number of patients who are
59:51actually surviving that long.
59:53With advanced kidney cancers,
59:54probably around 5 to 10%.
59:56Now if we contrast that with
59:58some of the modern therapies,
59:59we have the the ones that
01:00:00doctor Hurwitz mentioned,
01:00:01like Epilim AB and volume
01:00:03of these immuno therapies.
01:00:04We're starting to have longer follow-up,
01:00:06so five year follow-up of of
01:00:08those two drugs together.
01:00:09Some of you call that Nebo and hippie,
01:00:11and we see a dramatic improvement.
01:00:13Now, 40%,
01:00:15nearly half of people with
01:00:18advanced kidney cancer are alive.
01:00:20Five years later.
01:00:21This is an incredible improvement,
01:00:23but also,
01:00:24I think shows the road that we still
01:00:26need to take in the the sort of
01:00:28mountain we over we need to overcome.
01:00:3048 percent is incredibly
01:00:32different from 5 or 7%.
01:00:35But it's not 50%, it's not 70%.
01:00:37It's not 90%,
01:00:38and it's just we sell a huge way to go.
01:00:41And that's where really fundamental
01:00:42research into the disease comes into play.
01:00:45And so out of all of the
01:00:47potential areas of research,
01:00:48there's a couple that I
01:00:49really want to focus on,
01:00:50and these are some of the what I think
01:00:52of as this of critical questions.
01:00:53The big open questions in kidney cancer.
01:00:56One of them was actually brought
01:00:57up in the chat,
01:00:58which is a great segue.
01:01:00One is how do we select the right
01:01:01drug for the right patients?
01:01:02We know one drug might not work for everyone.
01:01:05This drug might drug.
01:01:06He might work for a group of people.
01:01:08Drug B might work for a different
01:01:09group of people.
01:01:10So how do we select that right
01:01:11drug for the right patient?
01:01:12Another word for that as biomarker,
01:01:14a test we can do.
01:01:16To try to select the right therapy.
01:01:19The second is how do we increase that
01:01:21number of patients with long term survival?
01:01:23I showed what I called the tale
01:01:24of the curve that was sort of
01:01:26flattening out overtime where you
01:01:28know nearly half of patients.
01:01:2948% of patients were alive five years later,
01:01:32but 48% is not 70%.
01:01:34So how can we continue to
01:01:35increase that number?
01:01:36And I would argue that understanding
01:01:38as as doctor Hertz was talking about
01:01:40how the immune biology of kidney
01:01:42cancer works and understanding other
01:01:44elements of biology to develop new
01:01:46therapies is going to be critical.
01:01:49As Doctor Hurwitz mentioned, getting anti PD,
01:01:52one therapy or immune based therapy is
01:01:54not really a standard in kidney cancer.
01:01:56Most patients with advanced clear cell kidney
01:01:59cancer would receive this but unfortunately
01:02:01many patients ultimately progress.
01:02:03I'll the the therapy stops working
01:02:05after a certain amount of time and so
01:02:07another huge challenge is what do we
01:02:09do next after we've we've used that
01:02:11that really potent medicine.
01:02:12What are other options that
01:02:13we might be able to do?
01:02:15And this is where thinking about
01:02:16new types of treatment and really
01:02:17understanding the disease.
01:02:18Biology is important.
01:02:20And lastly,
01:02:21I'll talk just very briefly about variant
01:02:23histologies or what's historically known
01:02:25as sort of non clear cell kidney cancer.
01:02:27I would think it's never good to be just
01:02:29defined by something that you're not,
01:02:30so this is the bucket of diseases
01:02:32that doctor Kenny was mentioning,
01:02:33which are individually uncommon,
01:02:36but in aggregate make up about
01:02:3925% of all renal cell carcinomas.
01:02:41And honestly we extrapolate a lot.
01:02:44We don't know how to treat individual
01:02:45ones nearly as well as we do clears.
01:02:47Also,
01:02:47we borrow a lot of the same drugs and so.
01:02:50How can we do a better job of
01:02:52treating those specific diseases?
01:02:54So we'll tackle these one at a time and
01:02:55it's gonna be a little bit of a worldwind.
01:02:57'cause again,
01:02:58I just want to give a sort of a hint
01:02:59of flavor of kind of the research
01:03:01going on so one is how do we select
01:03:03the right drug for the right patient?
01:03:04How do we develop biomarkers and the
01:03:06true answer is for kidney cancer.
01:03:07This has not been nearly as successful.
01:03:09If you think of things like advanced
01:03:11lung cancer, they have to have a much,
01:03:13much more success in picking up DNA
01:03:15changes or mutations that might serve
01:03:17as a marker for responsiveness to drugs.
01:03:20This is true of other tumor types as well.
01:03:23Kidney cancer has not been there.
01:03:24That,
01:03:24but my hope is that with a lot
01:03:26of the new tools that are coming
01:03:28out in the laboratory,
01:03:29that might ultimately translate into
01:03:30tools we can use to develop biomarkers
01:03:33and select and so I have a what I think
01:03:35is a little bit of a silly cartoon,
01:03:37but hopefully start hammers home.
01:03:39Why this is a really difficult problem.
01:03:41So we have two patients.
01:03:43One of them has a tumor that responds
01:03:46really well to therapy that's in blue.
01:03:48One has a tumor that in Portuguese resisted
01:03:50the therapy, and when we want to study it,
01:03:52to try to come up with a biomarker
01:03:54to try to figure out.
01:03:55What's going on now?
01:03:56If we look at the tumor itself,
01:03:58we think as a tumor is just one thing.
01:04:00It's not.
01:04:01It's actually a collection of many different
01:04:03types of cells within that tumor itself.
01:04:05Within that mass that we've
01:04:08seen as tumor cells munss else,
01:04:10other supportive cells,
01:04:12blood vessels.
01:04:13And there's a lot of heterogeneity
01:04:15differences between them.
01:04:16But what do we typically do
01:04:17when we want to study that?
01:04:18Even with things like sequencing,
01:04:20we put that all in a blender and what comes
01:04:22out on the other side looks like this.
01:04:24It's all looks.
01:04:25Pretty much the same when you blend
01:04:27it together and then we try to look
01:04:29back and squint and say why did one
01:04:31drug work for one patient and one
01:04:33drug not work for another patient,
01:04:35when in actuality we're really having a hard
01:04:37time after we blend everything together,
01:04:40picking out the individual cells in a tumor?
01:04:42The Kiwi that might be responsible
01:04:44for a drug working,
01:04:45or the strawberry that might be
01:04:47responsible for drug not working.
01:04:48And so this is a silly example,
01:04:49but kind of gets to the hint that the
01:04:51the idea that we really have to look at
01:04:53the cells individually and so there's
01:04:54now new tools that enable us to do that and.
01:04:57So we began to do that in various domains,
01:05:00and so we've we've started to do that and
01:05:03not the problem of this drug work or not.
01:05:06But how does a kidney cancer progress,
01:05:08and so the way we did that was to
01:05:09take patients and their tumors who
01:05:11had either early stage disease.
01:05:13As Doctor Kenny mentioned things that were
01:05:15really confined to the kidney locally.
01:05:17To answer that just began to spread,
01:05:19or patients who had tumors that were
01:05:21more advanced that really had spread
01:05:23to distant sites or or metastatic.
01:05:24And we actually broke those
01:05:26tumors down into individual.
01:05:27Cells and sequence 1 cell at a time and
01:05:30that's what this sort of cloud of dots shows.
01:05:32Each of these individual dots is actually
01:05:34one individual cell from a kidney tumor,
01:05:37and we can use that information to
01:05:39try to say what is actually there.
01:05:41What's different between an advanced
01:05:43kidney cancer versus an early
01:05:44cancer as it starts to spread?
01:05:46And how are the the communications
01:05:48that Doctor Hurwitz talked about?
01:05:49The how do the cells talk to each other?
01:05:51How does that differ between more
01:05:54advanced cancer in earlier stage cancer?
01:05:56That's what we've we've been working on.
01:05:58Now we're we're really working on
01:06:00the next step, which is to say,
01:06:01OK,
01:06:01can we use these newer and advanced
01:06:03tools to begin to ask those questions of
01:06:06why certain drugs work that they don't?
01:06:08What are the?
01:06:09What's the underlying biology?
01:06:10What's changing in the way?
01:06:12Cells talk to each other between a tumor
01:06:14that responds really well to immunotherapy,
01:06:16and one that unfortunately seems resistant.
01:06:18And that's work that our collaborative
01:06:20group with Doctor Hurwitz and and Doctor
01:06:22Ken and everyone is working on together.
01:06:26A second big open question
01:06:27is how do we do better?
01:06:29How do we get that 48% of
01:06:30patients who might be having a
01:06:32survival out of five years to
01:06:3470% to 80% higher and higher?
01:06:36And I think again the the
01:06:38key is really understanding
01:06:39the biology with the scenes.
01:06:43The the steps that need to happen
01:06:45for the immune system to actually
01:06:47work and recognize eliminate tumor.
01:06:49I think Doctor Howard did a
01:06:50really good job outlining that,
01:06:51but it's a really complicated process
01:06:53that the cancer has to actually
01:06:55release targets that the immune
01:06:57system can recognize that the immune
01:06:59system has to pick it up has to
01:07:01take it and deliver it to the right
01:07:03cell that's able to recognize it,
01:07:05but that immune cell has to
01:07:07then recognize it, turn on,
01:07:09travel back to the tumor,
01:07:11actually get into the tumor,
01:07:12and actually be able to attack him.
01:07:13Go to ourselves.
01:07:14There's a lot of things that have
01:07:16to go right and we really have to
01:07:17critically understand what are all the
01:07:19things that need to go right in order
01:07:21to effectively design immune therapies.
01:07:24As Doctor Hurwitz mentioned.
01:07:25These cells talk to each other
01:07:28and he mentioned he showed one
01:07:30really good example of EGF.
01:07:32I'm showing here probably 20
01:07:33examples of waste cells of the in the
01:07:36tumor actually talk to each other,
01:07:37and if you can believe it,
01:07:38this is actually a really simplified diagram,
01:07:41and so what's going on is a lot
01:07:42of lot of complicated cross stop,
01:07:45and this is what's going to be
01:07:47critical to understand how cells
01:07:48talk to each other and when a tumor
01:07:50responds really well to therapy,
01:07:52what are those connections?
01:07:53Or what conversations are happening and when?
01:07:56Appropriate therapy doesn't work.
01:07:58What are the different conversations
01:08:00that happen in that case?
01:08:02The other area that we go on,
01:08:03we've talked about a lot about
01:08:05Immunomodulation, which is, you know,
01:08:07either slamming on the gas pedal,
01:08:09things like Hydrocele 2,
01:08:10which really work to to turn on
01:08:12the immune system or taking away
01:08:14some of those checkpoints,
01:08:16immune checkpoint inhibition,
01:08:17which essentially serves to release or
01:08:19cut the brakes and let them use some.
01:08:21Let them use system go.
01:08:23I think moving forward we want
01:08:25to try to get a little bit more
01:08:26specific in the way to potentially
01:08:28do that is to add a steering wheel.
01:08:29If we think of those older therapies
01:08:31like I'll 2 is really the gas pedal
01:08:34and newer therapies like no volume AB
01:08:36and pembrolizumab as releasing the brakes.
01:08:38The question is,
01:08:39can we actually make the therapy more
01:08:40precise and add that steering wheel?
01:08:42There's lots of different ways to do that.
01:08:44This had been trials here at Yale and
01:08:46elsewhere that have explored cancer
01:08:47vaccines that really try to steer the
01:08:49immune system specifically towards the tumor,
01:08:51but there's really a whole world of ways.
01:08:54To really target the tumor directly,
01:08:56the tumor, the thing in the tumor that they
01:08:59need to recognize is called an antigen,
01:09:01and so can we design antigen directed
01:09:04therapies, things like CAR T cells,
01:09:06which are a lot in the news,
01:09:08vaccines, other approaches,
01:09:10and afterwards.
01:09:11Actually a lot of experience working
01:09:13with these cell based therapies in
01:09:15many different contexts to try to
01:09:17figure out how we can get towards
01:09:19antigen directed therapies.
01:09:21So, next briefly, you know we,
01:09:23we hope that we start off in a patient who
01:09:27has metastatic disease with an anti PD,
01:09:29one based therapy.
01:09:30But unfortunately for many patients
01:09:31that ultimately stops working.
01:09:33So what can we do after that?
01:09:34And that's where I think really
01:09:36thinking about the biology of
01:09:38the tumor is really important.
01:09:39Doctor Hurwitz really outlined
01:09:41very nicely the types of therapy
01:09:42that we use and when we think about
01:09:44the systemic therapies that we
01:09:46use for clear cell kidney cancer,
01:09:47there really are certain pillars
01:09:49that Doctor Harris talked about.
01:09:50There's immunotherapy,
01:09:51which I would argue is really
01:09:52a strong backbone.
01:09:53Now there's those anti angiogenic,
01:09:55those those pills that help to block
01:09:58new blood vessels from forming,
01:09:59essentially helping to starve
01:10:01the tumor of food.
01:10:02But we really need a new a new pillar.
01:10:05We need a new target and that's
01:10:06really been lacking and the way that
01:10:08we're starting to get there is by
01:10:10understanding the biology of the disease.
01:10:11And this is going to be a slightly
01:10:13more complicated version than
01:10:15Doctor Hurwitz had really kindly
01:10:16pointed out really nicely pointed
01:10:18out about how cells sense oxygen,
01:10:20and I bring up this slightly
01:10:21more complicated version,
01:10:22and this is a a system that
01:10:24was worked out by a number of
01:10:26investigators and actually led to
01:10:28the Nobel Prize in medicine in 2019.
01:10:30Just because it is complicated.
01:10:32And that's why I think the fundamental
01:10:34research that the basic biology so important,
01:10:37because that's what ultimately
01:10:38leads to these new therapies.
01:10:40So as Doctor Hurwitz had mentioned.
01:10:42Under normal oxygen condition,
01:10:43so we have oxygen floating around normoxia,
01:10:46then VHL is active and it helps to
01:10:49basically breakdown thrown to the trash.
01:10:52Certain proteins like HIF two and
01:10:54HIP two ends up being really a key
01:10:56protein for clear cell kidney cancer.
01:10:59In normal parts of our body.
01:11:00If we don't have enough oxygen
01:11:02then the HL is not active,
01:11:04it's turned off as Doctor Hurwitz
01:11:06said this hip two is then it's
01:11:08not thrown in the trash anymore.
01:11:10It can go and do its job which is
01:11:11to make new blood vessels or empty.
01:11:13Angiogenesis helped the cells
01:11:15grow and survive.
01:11:17In clear cell kidney cancer,
01:11:19we know that this VHL protein is missing
01:11:21and so this hip is on all the time
01:11:23and so even when it's not supposed to,
01:11:25the cells are grown new blood vessels.
01:11:28They're growing themselves.
01:11:29They're surviving.
01:11:30They're becoming clear cell kidney cancer,
01:11:32and so this.
01:11:33Now when we know we know this biology,
01:11:36it's the natural question.
01:11:37Can we just have a drug that
01:11:39might help to shut off?
01:11:40If too that might help to stop all these
01:11:43things that are happening downstream,
01:11:45and that's where a new drug
01:11:46belzu dibbin which is.
01:11:47Now approved for specific patients.
01:11:49Really,
01:11:50for patients with hereditary
01:11:51kidney cancer with VHL syndrome,
01:11:53but is being actively tested
01:11:55more broadly and preliminarily,
01:11:56has some encouraging results.
01:11:58Really acts to block this hip
01:12:00too and stop those down trip signals,
01:12:03and so this is just an example
01:12:04of how the basic biology really
01:12:06understanding of fundamental process
01:12:08like how our cells sends oxygen leads
01:12:10to advancements in kidney cancer.
01:12:14The other thing I just want to briefly
01:12:16mention is I talk a lot about new
01:12:17drugs and new technologies and those
01:12:19are things that I'm excited about,
01:12:20but I think there's also the
01:12:21question can we just optimize?
01:12:22Can we actually do better
01:12:23with the things that we have?
01:12:25And this is something from when I
01:12:27was at at Dana Farber in the past.
01:12:28That always sort of struck me.
01:12:29This is borrowing a lesson
01:12:31from pediatric leukemia,
01:12:32so these are survival curves that children,
01:12:34unfortunately with pediatric
01:12:36leukemia and trials done at Dana
01:12:38Farber in the nineteen 1973,
01:12:40nineteen 7719, eighty 1985.
01:12:43So over the course around 15 years.
01:12:45And we can see this is a dramatic
01:12:48improvement that in the 1973 less than
01:12:50half of fewer than half of children with
01:12:52leukemia were surviving by the mid 80s,
01:12:54nearly 80% were what I found so
01:12:57remarkable about this is that
01:12:58this was a period where there was
01:13:00actually no new drug discovery.
01:13:02This is all just optimizing
01:13:03the drugs that they had,
01:13:05and they had this dramatic
01:13:07improvement in survival,
01:13:08and so I think it's sometimes not.
01:13:10As you know, it's not as hot a topic to say.
01:13:11Let's just optimize what we have,
01:13:13but that sometimes is one of
01:13:15the most effective things.
01:13:16And that started to be done in kidney cancer,
01:13:18particularly for patients who had
01:13:20received immunotherapy in the past.
01:13:22People are beginning to ask,
01:13:23can we actually just optimize
01:13:24and tweak things?
01:13:26You know,
01:13:26a standard after someone got immune
01:13:28therapy would be to get a drug like
01:13:30tablets anti neighbor tivozanib.
01:13:31So asking really simple
01:13:33and fundamental questions.
01:13:34Can we actually add another
01:13:36immunotherapy agent to that?
01:13:38Same that same drugs?
01:13:40Or having Kevin cabozantinib alone,
01:13:41can we actually add at Tesla Lizama?
01:13:43Have another immunotherapy and
01:13:44get a better response and how
01:13:46patients to live longer.
01:13:47There's multiple trials
01:13:48that are exploring this,
01:13:50but I think goes up with
01:13:51the overall principle.
01:13:52Can we optimize the tools that we have?
01:13:55And then,
01:13:55very briefly,
01:13:56how do we treat these variant histologies?
01:13:58Essentially everything I've
01:13:59talked about so far is really
01:14:01for clear cell kidney cancer,
01:14:03but we know that 25% one and four renal
01:14:05cell carcinomas are not clear cell.
01:14:07There are these variant histologies
01:14:09and you just look at them and
01:14:11they are dramatically different,
01:14:12so these are what they look like.
01:14:15Both when you look at the tumor
01:14:17itself and then next to it is what
01:14:18they look like under the microscope
01:14:20and I just have a couple of examples
01:14:21of papillary tumor under microscope.
01:14:23This one that type one.
01:14:25This one is,
01:14:26which is historically called a Type 2.
01:14:28This is a chromophobe and you don't
01:14:29have to be a pathologist to look at
01:14:31these and say they look dramatically,
01:14:33dramatically different.
01:14:34They're really not the same disease.
01:14:37And in a table similar to what doctor
01:14:38Kenny and Doctor Hurwitz had shown,
01:14:40these have a different biology
01:14:41and so lumping them all
01:14:42together and assuming they will act in
01:14:44the same way and will respond to the exact
01:14:46same treatment is probably just not right.
01:14:48We really have to think about
01:14:49how to do this intelligently,
01:14:51and I think the field is really really
01:14:53coming around and beginning to do this.
01:14:54I think for the first time there
01:14:56was a large trial is a large base,
01:14:58two trial that really targeted specifically
01:15:00papillary cancer and had a positive
01:15:02result that was really encouraging,
01:15:04and this has paved the way for new trials.
01:15:06This is just.
01:15:07One of many that are are starting to emerge.
01:15:09This is something called the CIMETTA trial.
01:15:11This is mostly when actually out of Europe,
01:15:13but it's a trial where it's for patient,
01:15:15specifically with papillary cancer,
01:15:16and specifically even that
01:15:18Type 1 papillary cancer.
01:15:19So those that have a specific alteration
01:15:22in the DNA ones that are driven by
01:15:25this protein met and those those
01:15:27patients which are very specifically
01:15:29selected then are getting one of
01:15:31three different types of therapies,
01:15:33and so this is just one example
01:15:34of an ongoing trial,
01:15:35but gets the the overall point.
01:15:37We have to better understand these tumors.
01:15:39These variant histologies and that
01:15:40we can't always lump them together.
01:15:42We we really have to think about
01:15:44how they're different and unique
01:15:46and treat that individual biology.
01:15:48And so that's briefly what we talked about.
01:15:49Some of the big open questions and
01:15:51research biomarker developments like
01:15:52the right drug for the right patients,
01:15:54getting more patients to survive long
01:15:56term really hopefully get into that.
01:15:58That word cure for more and more
01:16:00and more patients.
01:16:01How can we treat patients for which the
01:16:03initial therapies haven't worked as well?
01:16:05And how can we treat that one out of
01:16:07four patients that don't have that
01:16:08the classic clear cell kidney cancer
01:16:10and the way we're hoping to do that
01:16:12and and Yale by working between
01:16:14physicians and and lab based scientists.
01:16:17The way we're really hoping to do that.
01:16:18Is through really a process of
01:16:20bedside to bench and back again?
01:16:22Kind of research and the the basic
01:16:24idea here is that we work with
01:16:26patients who are who are interested
01:16:28in contributing to research.
01:16:29We study their kidney cancer.
01:16:31Specifically,
01:16:31we go back through the lab and we
01:16:33really try to learn things about their
01:16:35kidney cancer about kidney cancer.
01:16:37More generally,
01:16:38we think about what are the new
01:16:40questions that we have to answer
01:16:42about improving immuno therapies
01:16:43and other types of treatments.
01:16:45We try to use that in a laboratory to
01:16:47figure out how we're going to design better.
01:16:49Diagnostic tests,
01:16:50better biomarkers,
01:16:51better therapies and then try to
01:16:53actually bring that back to the
01:16:55patient and translate that into better
01:16:57therapies and better tests for patients.
01:16:59And it's an iterative process
01:17:00really going back and forth to try
01:17:02to do this in continuous fashion,
01:17:04and so with that I I'm thankful
01:17:06to all the patients and families
01:17:09and caregivers
01:17:10who really this research is only
01:17:12possible because of their generosity
01:17:13and the medical providers that really
01:17:15make it happen and happy at this time
01:17:17to hopefully answer a few questions.
01:17:20That's fantastic.
01:17:20I think there's a little bit of time,
01:17:22and then we'll go to Claire.
01:17:23I don't care that I wanna know
01:17:25what she's going to say so.
01:17:26So let me start with some of the questions.
01:17:29So one of the questions wasn't movie.
01:17:30I'll be interesting to
01:17:31see to hear your answer,
01:17:32'cause our answers might differ
01:17:34slightly is 1 combination of an
01:17:36inib and a new mab better than
01:17:38another for cancer that has spread.
01:17:40So let me just clarify for one second,
01:17:41for for the people there that
01:17:43we generally start treatments
01:17:44with metastatic cancer with a
01:17:46combination of two medications and
01:17:47often those combinations are one
01:17:49of those pills we talked about.
01:17:50The anti VHL type well.
01:17:52The anti that shaft pathway ones
01:17:54and one of the immune therapies.
01:17:57So David are the combinations
01:17:59different from each other or not?
01:18:02It's a great question.
01:18:03I think if you ask 10 different kidney
01:18:05cancer experts across the country,
01:18:07you're gonna get probably three
01:18:09or four different answers.
01:18:11But I'll say a couple things.
01:18:12So I sort of lumped them
01:18:14together into two big buckets.
01:18:16Are you going to get 2
01:18:17immunotherapy drugs together?
01:18:18That's one option,
01:18:19or are you going to get one immunotherapy
01:18:21drug and one of those blood vessel
01:18:23blocking drugs and anti angiogenic?
01:18:25That's the other bucket.
01:18:26Now if you're in this bucket
01:18:28of A1 immunotherapy and a a
01:18:31blood vessel blocking drug.
01:18:33Are there differences between them?
01:18:34There's actually 4
01:18:35regimens that are approved.
01:18:36The answer is is probably slight
01:18:38differences between them,
01:18:39but it's probably pretty slight.
01:18:40I think the things that matter
01:18:42probably more than anything else is.
01:18:44If you're within that class of drugs,
01:18:46the physicians comfort
01:18:47level in prescribing them.
01:18:48So people who prescribe
01:18:49cabozantinib alot are going to
01:18:51probably prescribe Cowboys anthem,
01:18:53and that's probably a better
01:18:54option than people who prescribe.
01:18:55That's it novel Otter, another drug.
01:18:57And so I think once you're in that class,
01:18:58there might be subtle differences,
01:19:00but they're by and large pretty
01:19:02pretty similar, especially.
01:19:03The latest generations there might be
01:19:05differences in how toxic they are,
01:19:07meaning how many side effects
01:19:09they might cause,
01:19:09and that might help the guide
01:19:11which among those I think a big
01:19:12question is how do you choose
01:19:14between those two big branches.
01:19:15I think that's a bigger question.
01:19:16How do you choose between 2 immune
01:19:18therapies and an immunotherapy?
01:19:20And and I think again you can go
01:19:22to many experts and there's no.
01:19:24There's no trial comparing them head-to-head,
01:19:26so no one,
01:19:27no one can tell you that answer for sure,
01:19:29but I'll give you sort of my my two cents.
01:19:31I think the thing that's been
01:19:32transformative about I mean therapy.
01:19:34Is not only that they lead to
01:19:35tumor shrinkage,
01:19:36but really that for some patients
01:19:37they lead to a long term survival.
01:19:39Maybe even for that subset
01:19:41of patients a cure.
01:19:42And while we don't know this for sure,
01:19:45I think there's there's some reason
01:19:46to think that having those two
01:19:48immune therapies together might
01:19:50actually increase the chance of
01:19:51having that longer term survival,
01:19:53and so all other things being equal,
01:19:55I tend to lean towards that.
01:19:57But it's not for everyone.
01:19:58And then the question is why one
01:20:00is those those can in certain
01:20:01ways be more toxic.
01:20:02They have more immune related side effects.
01:20:05That's a. That's a really important thing.
01:20:07The second is.
01:20:08While they might work better,
01:20:10arguably that's arguably in the
01:20:12long term in the short term,
01:20:14they probably don't shrink
01:20:15the tumor quite as well,
01:20:16and so there are patients who
01:20:18unfortunately have disease that
01:20:20might be really rapidly grown,
01:20:21or they might have a lot of
01:20:22symptoms from their disease,
01:20:23where the most important thing is really
01:20:25shrinking it as soon as possible,
01:20:27in which case having to immunotherapy's
01:20:29might always be the best option.
01:20:30So the overall answer is it tends to
01:20:32be a patient, specific conversation.
01:20:34At least that's my. My two cents,
01:20:36but Michael curious with your thoughts are
01:20:38I'm actually very relieved.
01:20:39I don't have to say anything
01:20:40'cause that's the exact answer
01:20:41I would have liked to give.
01:20:43I mean, almost you know word for word,
01:20:45except except said better so
01:20:46that that that's fantastic.
01:20:48That makes me very happy,
01:20:49but it's absolutely true that
01:20:50you can talk to 10 different
01:20:51kidney cancer docs and get 10
01:20:53different similar similar answers,
01:20:55usually alright.
01:20:56The second question is when will
01:20:59real information as to biomarkers
01:21:01and patients and they're likely
01:21:02response to immune therapies
01:21:04or to targeted therapies.
01:21:05Happen and what makes one patient
01:21:07responder versus something
01:21:08versus unlikely to respond?
01:21:11Yeah, it's a. It's a great
01:21:13question and one that I
01:21:14wish we had the answer to today and
01:21:15so the the real answer is we don't
01:21:17have read biomarkers right now,
01:21:19and I think we we absolutely
01:21:20need to do better and think
01:21:22about every possible domain.
01:21:24Honestly, one of them may
01:21:25be the better biomarkers.
01:21:26That's out there is not any fancy
01:21:28sequencing that I talked about is
01:21:30actually looking under the microscope
01:21:32we had talked about these sarcomatoid
01:21:35and rhabdoid tumors before.
01:21:37Those are ones which historically
01:21:38unfortunately have not responded
01:21:40nearly as well to the pills.
01:21:41Does anti angiogenic get medicines,
01:21:44but for some reason seem to have a much,
01:21:46much better response to immunotherapy's
01:21:48the number of actually patients
01:21:49who have a complete response being
01:21:51the tumor seems to just disappear,
01:21:53is actually higher in those patients
01:21:55with sarcomatoid features because
01:21:56you only really find by looking
01:21:58under the microscope compared to
01:22:00other patients with kidney cancer,
01:22:02and so sometimes the old traditional
01:22:04tests are still the best ones,
01:22:06but I wish I could say today we
01:22:08have the absolute molecular test
01:22:10that tells us about the drug works.
01:22:12Or doesn't we're working on it,
01:22:14but we don't have it yet.
01:22:16OK, and two more questions.
01:22:17One is are there metastasis into lung
01:22:21and liver still for chromophobe? Like,
01:22:24yeah, yeah, absolutely so.
01:22:25It's this is, I think,
01:22:27a common question terminology.
01:22:28If someone has a kidney cancer
01:22:30but then move somewhere else,
01:22:31it's moved to the lungs.
01:22:32Is it still kidney cancer?
01:22:34And really it matters less where it is
01:22:36and more where it came from in terms
01:22:38of how we define the tumor and how,
01:22:40how those tumors might
01:22:41actually respond to therapy.
01:22:43So if it's a chromophobe that then
01:22:44moved to the lungs and they they did
01:22:46a biopsy or surgery and really looked
01:22:48it under the microscope and it looks
01:22:50the same but the doctors are really
01:22:51confident it came from the kidney.
01:22:53That would still be the same cancer.
01:22:55Yeah? And it's although it's
01:22:57rare homophobes do metastasize.
01:22:59You know, we we see it to to
01:23:01answer that question and then
01:23:03I think I'm sorry.
01:23:04I think really important point about
01:23:06Chromophobe's is that it's much more
01:23:08common for patients who have metastatic
01:23:10chromophobe kidney cancer to have had
01:23:13metastases at the time of diagnosis.
01:23:15It's much less common for
01:23:18someone who's had on imaging.
01:23:20It looks localized they've had surgery.
01:23:22It's much less common for those patients.
01:23:24To develop cancer spread and you know,
01:23:28I think for a lot of our patients
01:23:30who have had surgery for,
01:23:33you know, a large or higher stage.
01:23:36But localized chromophobe kidney cancer.
01:23:38I think it's really important to know
01:23:41that those patients often do very
01:23:43do quite well and don't necessarily
01:23:45have some of the same level of
01:23:47risks as other more aggressive
01:23:48types of kidney cancers like as
01:23:51like a high grade sarcomatoid,
01:23:53clear cell kidney cancer.
01:23:54For instance,
01:23:56it's really important point.
01:23:59So the last question,
01:24:00which I don't exactly understand,
01:24:01but I'll say it word for word and
01:24:03it's is as a stage four Survivor
01:24:05now 18 years thanks to surgery
01:24:08and high dose interleukin 2.
01:24:10Why not review the value of that
01:24:12treatment in light of our better
01:24:13understanding of kidney cancer?
01:24:16So my search sense I could be wrong is
01:24:20that maybe why not go back to Hydrocele
01:24:222 and surgery things that might have
01:24:24worked in the in the past and I I
01:24:26think it's a really good question.
01:24:27If you know we we look back and high dose
01:24:30is not something that's commonly used,
01:24:32but there were actually patients who
01:24:34had a really long term response.
01:24:35Probably cure.
01:24:36It was probably on the order of
01:24:38around 5 to 7%, so not frequent,
01:24:40and it's something that can be really toxic,
01:24:42so it's typically administered
01:24:43and it really monitored setting
01:24:45'cause people can get very sick.
01:24:46So the question is, why don't we do it more?
01:24:48More commonly I think the short answer is 1.
01:24:51We have tools that we think
01:24:52are maybe slightly better.
01:24:53These immune checkpoint drugs and two
01:24:55was actually being studied are similar
01:24:57medicines to high dose IL 2 but that
01:24:59have been modified to try to make them
01:25:01a little bit less toxic and maybe a
01:25:03little more efficacious and so those
01:25:05drugs are actually these modified.
01:25:07I'll twos are actually in
01:25:08clinical trials now.
01:25:10Yeah, so I would. I would.
01:25:11I would add that a little bit which
01:25:12is that it is happening is the point.
01:25:14There are a bunch of drugs out there
01:25:16that are thought to be better ILD who's
01:25:18but but use the I O2 biology that are
01:25:21being studied currently and they're
01:25:22going to be doing it in combination
01:25:24with the other types of therapy.
01:25:25So it's all happening and
01:25:27hopefully it'll it'll.
01:25:28It'll be great.
01:25:29Alright, let's move on to Eric Healey.
01:25:32One more geneticists and one comments.
01:25:36What was that? Oh
01:25:38no, sorry there was just one
01:25:39more question in the Q&amp;A and
01:25:40it just said asked about that.
01:25:42How severe are the side effects of
01:25:44the oral medications for kidney
01:25:45cancer compared to what we think
01:25:47of as traditional chemotherapy,
01:25:49nausea, hair loss, things like that.
01:25:52So so in brief, they're quite different,
01:25:55so and and and and it it depends so so.
01:26:01I think the the they're not as bad.
01:26:03Acutely I would say,
01:26:04although other people could disagree with me,
01:26:06but the problem is that you
01:26:07take him for a long time.
01:26:08You take him every day and they can
01:26:09be incredibly wearing and some people
01:26:11just do have very bad side effects,
01:26:12but the side effect profile is
01:26:14quite different. I would say the
01:26:16number one thing is GI issues.
01:26:18A lot of diarrhea for some people,
01:26:20maybe a lot of rash for some
01:26:22people that can be quite difficult.
01:26:25Appetite can go down, there can be nausea.
01:26:27You know a lot of fatigue can happen.
01:26:31And so.
01:26:32It it's it's almost it's very
01:26:34hard to compare because.
01:26:36It's a chronic thing,
01:26:38usually versus chemo,
01:26:40which is sort of happens and then
01:26:41gets better happens and gets better.
01:26:45I don't there's probably a better
01:26:46answer out there. I don't know David.
01:26:48You have a better way to put
01:26:50no, I think that's sort of short,
01:26:52but more severe versus longer,
01:26:55but kind of wearing is is probably
01:26:56a really good thing and everyone
01:26:58everyone sort of is different in terms
01:27:00of the side effects they experience
01:27:02I I think probably on average people
01:27:04think of these as being, you know,
01:27:06they feel less bad than than the
01:27:08conventional cytotoxic chemotherapy
01:27:09that would make people lose their
01:27:11hair and make people nauseous.
01:27:12But you can imagine it's one thing to.
01:27:14Have that dose of chemotherapy and
01:27:16feel really sick for a couple of weeks
01:27:18versus something that you know maybe
01:27:20makes you feel a little bit tired but
01:27:22kinda wears on day after day, after day,
01:27:24that after months or years of it.
01:27:25It might sort of build up that
01:27:27I think that's the difference,
01:27:28and so it's you're absolutely.
01:27:29I think it's hard to compare.
01:27:32Let's move on.
01:27:33So yes, someone said that hand
01:27:35Foot syndrome is not really.
01:27:36It absolutely is so.
01:27:38So there is a question,
01:27:40but you're going to hopefully
01:27:41answer it 'cause it's one of
01:27:42the genetic predispositions
01:27:43for RCC and other things so.
01:27:46Started so my name is Claire Healy.
01:27:49I'm one of the genetic counselors
01:27:51in the smilow cancer genetics
01:27:53and prevention program.
01:27:55Can everyone see my slides?
01:27:58Alright, perfect, so I'm going to do
01:28:00just a brief overview of hereditary
01:28:03kidney tumor and cancer syndromes.
01:28:05It would be impossible to do a deep
01:28:07dive in a short period of time,
01:28:09but I'll do my best to give
01:28:11kind of a brief overview,
01:28:13so we'll start just by kind
01:28:16of pointing out that while.
01:28:18We're gonna talk about hereditary
01:28:20kidney cancer syndromes.
01:28:21Hereditary hereditary kidney cancer and
01:28:23tumor syndromes are actually fairly rare,
01:28:26and most cancer is not hereditary or genetic.
01:28:30So most cancer 70% of cancer
01:28:33is actually sporadic,
01:28:35and that just means that it's caused by
01:28:37things like the normal aging process,
01:28:40overtime, lifestyle factors,
01:28:43environmental exposures,
01:28:44and in most cases when we look
01:28:47at a patient's personal history,
01:28:49family history,
01:28:50when the cancer sporadic will
01:28:51expect to see those cancers
01:28:53occurring kind of at at later ages.
01:28:55General population ages.
01:28:56When we look at the family history,
01:28:59we'll expect to see.
01:29:01A random mix of cancer types in the family.
01:29:04Another 20% of cancer is explained
01:29:08by a familial predisposition,
01:29:10so these are families where we might
01:29:13see multiple people in the family who
01:29:16are developing the same type of cancer,
01:29:19and so we might see.
01:29:22And a higher than average risk
01:29:24for a certain type of cancer.
01:29:27But we would still expect to see
01:29:29most of those cancers developing
01:29:32average population ages.
01:29:34In most cases we wouldn't see
01:29:36rare or unusual types of cancers,
01:29:38and these are really clusters of
01:29:41cancers that are likely explained by
01:29:43some shared genetic risk factors.
01:29:46But alongside a shared combination
01:29:49of lifestyle and environmental
01:29:51exposures as well.
01:29:53And then really only 5 to 10%
01:29:55of her cancer is explained by
01:29:59a Hereditary Cancer syndrome.
01:30:01And so these are situations where
01:30:04there is a greater lifetime risk of
01:30:07cancer that cancers are typically
01:30:10diagnosed at younger than expected ages.
01:30:13There's a greater chance of
01:30:15developing a second cancer,
01:30:17and we usually see more rare
01:30:19types of cancers as well.
01:30:21And in these families,
01:30:22we may see the same type of cancer or
01:30:26related types of cancers clustering together.
01:30:29So in terms of what we look for,
01:30:31what you should look for,
01:30:33what your doctors are looking for,
01:30:34and what your genetic counselors are
01:30:36looking for to kind of give clues
01:30:39as to whether there's a hereditary
01:30:41predisposition for cancer in the family.
01:30:43Are things like cancers that are
01:30:45diagnosed at earlier than expected ages?
01:30:48So for kidney cancer we usually
01:30:50say that's under the age of 4746.
01:30:53Forty seven.
01:30:53I know that sounds like sort of a
01:30:57very arbitrary and specific number,
01:30:59but there is research out there that
01:31:02says really anything under 4647
01:31:04is where the risk for Hereditary
01:31:07syndrome really starts to increase.
01:31:09We would also expect to see multiple
01:31:11family members on the same side
01:31:13of the family with this same type
01:31:16of cancer or related type of cancer
01:31:18or tumors, so this might be a mother
01:31:20and a child who have both had the same
01:31:23type of kidney cancer or two siblings
01:31:26with the same type of kidney cancer.
01:31:29And then we can see rare cancers or
01:31:33rare tumors such as angiomyolipomas
01:31:35or chromophobe tumors that have
01:31:38already been mentioned tonight.
01:31:40And we might also see a person who's
01:31:43developing multiple cancers or tumors.
01:31:45Sometimes this is multiple
01:31:46tumors in the kidney,
01:31:47but other times it's multiple
01:31:49different types of cancers or tumors.
01:31:52And rare benign tumors.
01:31:53So in a lot of our hereditary
01:31:56kidney cancer syndromes,
01:31:58these are going to be rare benign tumors
01:32:00that are developing in the kidney,
01:32:02but also rare benign tumors that
01:32:05are developing on this skin.
01:32:07Sometimes those are lesions on the
01:32:09skin that might be very subtle and that
01:32:12you might not even notice yourself,
01:32:15but that a dermatologist might
01:32:17be able to see.
01:32:18Other times,
01:32:19those might be things on your skin that are,
01:32:21you know, sort of just skin colored.
01:32:23But maybe you notice that they're really
01:32:25sensitive to the cold or when you touch them.
01:32:28They're a little bit painful.
01:32:30Sometimes these rare tumors are things
01:32:32that develop in the brain or in the lungs,
01:32:34and so they're not things that
01:32:36you would encounter,
01:32:37kind of in the the general
01:32:40population very often.
01:32:42And when we talk about
01:32:44hereditary syndromes really,
01:32:46what we're talking about and what
01:32:47what's already been mentioned tonight,
01:32:49are these genes that normally are
01:32:51kind of helping to prevent cancer,
01:32:53so they're keeping the cells in our body,
01:32:56kind of growing and dividing
01:32:58into really regimented way.
01:32:59And so,
01:33:00like what's been mentioned previously,
01:33:03most of the time people are born with two
01:33:06healthy working copies of those genes,
01:33:08and when that's the case,
01:33:10the way they develop a tumor.
01:33:12Or a cancer?
01:33:13Is that both copies have to become damaged,
01:33:17or what we call mutated overtime to
01:33:20allow the cell to start growing,
01:33:23dividing out of control,
01:33:24forming that tumor,
01:33:25and eventually the cancer.
01:33:27In individuals who have an inherited
01:33:30cancer predisposition syndrome,
01:33:33what happens is they actually
01:33:35start their life one step into
01:33:37that process so they are born with
01:33:41one healthy working copy of these
01:33:44genes and then the other copy,
01:33:46and every cell of their body
01:33:48contains a mutation and so they're
01:33:51sort of down one line of defense
01:33:53when we think about cancer,
01:33:55because now it's going to take just one.
01:33:58Random event to occur before the
01:34:00tumor or the cancer can develop,
01:34:03and that's why we would expect to see
01:34:05younger ages at the time of diagnosis.
01:34:07A higher cancer risk overall,
01:34:10and why we can see multiple tumors and
01:34:14multiple different areas of the body.
01:34:17So this is a very busy slide,
01:34:19and I apologize that it's so cluttered.
01:34:22But when we think about our hereditary
01:34:25kidney tumor or cancer syndromes,
01:34:27these are the most common ones.
01:34:29There are some other ones,
01:34:30but these are the the ones
01:34:32we think about the most.
01:34:34And you can see that when your
01:34:36doctors are meeting with you,
01:34:37or if you meet with a genetic
01:34:40counselor really what we're thinking
01:34:41about first are what type of kidney,
01:34:44tumor or cancer do you have that helps
01:34:48us kind of narrow down what syndrome
01:34:50might might we be thinking about?
01:34:52So we've already talked about VHL tonight,
01:34:55which is associated with the
01:34:57clear cell type of kidney cancer,
01:35:00but we also have hereditary syndromes
01:35:02that are associated with other types.
01:35:04I have kidney cancers like papillary
01:35:07kidney cancer, chromophobe tumors,
01:35:09the angiomyolipomas that were
01:35:12mentioned earlier tonight.
01:35:14And then so that helps us
01:35:15kind of narrow down.
01:35:16OK, What syndrome are we thinking
01:35:19about in that individual or the family?
01:35:21And then we think about?
01:35:22Are there any of those other
01:35:24features that we would expect to see
01:35:26in that individual or the family?
01:35:28Like some of those non cancerous or the
01:35:32benign tumors in other areas of the body?
01:35:34So when you meet with a genetic counselor,
01:35:37we spend a lot of time talking about your
01:35:40medical history and your family history.
01:35:42We ask you what feels probably like
01:35:44a laundry list of questions about.
01:35:46Different aspects of your medical
01:35:48care and your family members.
01:35:50Medical history.
01:35:50But really,
01:35:51the reason we're asking those detailed
01:35:53questions is 'cause we're trying
01:35:55to narrow down as much as possible.
01:35:57What hereditary syndrome?
01:35:59What might we be thinking of?
01:36:03And then just in terms of basics
01:36:05of genetic testing,
01:36:06if you are thinking about genetic testing
01:36:08and you do meet with a genetic counselor,
01:36:11a genetic counselor will kind of
01:36:13go over different test options
01:36:14with you insurance coverage.
01:36:16Answer all of those questions.
01:36:18But just to give you a little
01:36:20bit of background,
01:36:20genetic testing can be completed
01:36:22from blood or from saliva.
01:36:25It is covered by most insurance companies,
01:36:28especially if you have a personal or
01:36:31a family history that's suggestive
01:36:33of a hereditary.
01:36:34Cancer syndrome, so again,
01:36:35if you're young when you're diagnosed,
01:36:38if you have a family history of a
01:36:40first or second or relative who was
01:36:42young when they were diagnosed with cancer?
01:36:44If you have some of those benign rare tumors,
01:36:47all of those things are going to suggest
01:36:49that there is a hereditary risk,
01:36:51and in most cases you will have
01:36:54coverage for genetic testing.
01:36:56Luckily,
01:36:56the price of genetic testing has come down,
01:36:59so if in the unlikely event you do
01:37:01not have coverage for genetic testing,
01:37:04most of the time we can complete
01:37:06that genetic testing for an out
01:37:09of pocket cost of around $250 and
01:37:11a lot of the genetic testing
01:37:13laboratories that we use do offer
01:37:15patient financial assistance as well.
01:37:17And there are federal laws that prohibit
01:37:20genetic discrimination by health
01:37:22insurance companies and employers,
01:37:24with some rare exceptions,
01:37:27particularly for our active
01:37:29duty service members.
01:37:31And that was my last slide.
01:37:37I was on mute. That's fantastic.
01:37:38Excellent. It was great.
01:37:39So in in there there are questions
01:37:42that are absolutely up your alley.
01:37:44So the first question is what are the
01:37:47the genetic predispositions for RCC?
01:37:49And now you know the
01:37:50answers to the others too.
01:37:51And skin or bladder cancer.
01:37:53So there's not necessarily one syndrome
01:37:56that connects all three of those together.
01:38:00But there are a number of
01:38:02hereditary kidney cancer syndromes.
01:38:03Some of those increase the
01:38:05risk for Melanoma as well.
01:38:06So if we're talking about a skin cancer,
01:38:08that's Melanoma.
01:38:09That could be a concern.
01:38:12There is a hereditary cancer
01:38:14syndrome that does increase
01:38:15the risk for bladder cancer and
01:38:18collecting duct tumors of the kidney.
01:38:20So if you have a family history or
01:38:22personal history of all of those cancers,
01:38:24good idea to ask for or for
01:38:26all to a genetic counselor.
01:38:28Great and second question was
01:38:31my dad had a tumor, no, no.
01:38:34There's another one. Sorry.
01:38:35My brother and I were both diagnosed
01:38:37with clear cell kidney kidney cancer.
01:38:39We both completed genetic
01:38:41testing with no concerns.
01:38:42How concerned should we be
01:38:44for our children inheriting
01:38:45clear cell kidney cancer?
01:38:47So one thing that I would say
01:38:49is just like most medicine,
01:38:51genetic testing gets better with time.
01:38:53So if your genetic testing
01:38:55was performed a while ago,
01:38:56we likely have newer genetic testing
01:38:59technology that can evaluate the
01:39:01same genes but pick up mutations that
01:39:04may have been missed previously.
01:39:06So if your genetic testing
01:39:08was completed a while ago,
01:39:09good idea to contact whoever
01:39:11performed that genetic testing or
01:39:13ask your doctor for a referral to
01:39:15a genetic counselor to see if.
01:39:17Updated testing with the appropriate.
01:39:20In families where there are multiple
01:39:23relatives with a tumor type where we do
01:39:27not identify a genetic predisposition,
01:39:30it doesn't mean that one doesn't exist.
01:39:32We don't know of all genes that are
01:39:35associated with these hereditary cancer
01:39:37syndromes and also there's still that
01:39:39risk of a familial predisposition,
01:39:41so not one single genetic factor
01:39:43but a combination of factors.
01:39:45So in that case,
01:39:47with two relatives closely related to
01:39:49one another with the same tumor type.
01:39:52I would still estimate that their risk
01:39:54for other family members to develop
01:39:56that same tumor type would be higher
01:39:58than in the general population.
01:40:01And that that's a great answer,
01:40:03I let me let me add one or two things and and
01:40:05other people can correct me if I'm wrong.
01:40:07You know, sometimes it helps to know a
01:40:09little bit more about the situation so.
01:40:12You know, are the tumors bigger? They small.
01:40:15How old were you when you got that?
01:40:17If if if you're both 80 years old,
01:40:20still it's it's.
01:40:21It's not super common that you both
01:40:22have that, but it may not be so
01:40:24uncommon if you're both 55 years old.
01:40:26That's different so but but but
01:40:29I think that point you made is so
01:40:31important that just because we don't.
01:40:33Have a name for.
01:40:34It doesn't mean there isn't a genetic
01:40:35thing out there that we don't know of yet.
01:40:37Is that yeah, and
01:40:39doctor Kenny is reminding me that
01:40:41I said a while ago but didn't
01:40:43really define what that was,
01:40:45so anything more than five years ago,
01:40:48we always recommend our patients
01:40:49contact us every five years to see
01:40:52if there's any new genetic testing
01:40:54technology that they would be worthwhile
01:40:56updating their genetic test with.
01:40:59And and so this person actually
01:41:00answered and said they're in their 50s.
01:41:02And and my answer to that is,
01:41:05go see Claire because you know what
01:41:08you're going to do and maybe you would
01:41:10say this already is that you do a
01:41:12whole history about what's going on
01:41:13with the family and all those things.
01:41:15You get a lot more information
01:41:17by that, right?
01:41:18Yeah, absolutely.
01:41:18And even if there's not
01:41:21updated genetic testing,
01:41:22we can talk about risks to relatives,
01:41:25what those risks may be,
01:41:27and can also help make connections for.
01:41:29Unaffected people in the family
01:41:30with high risk providers who
01:41:32may be able to offer screening.
01:41:35OK, and the last
01:41:36another really important thing to think
01:41:38about too is shared exposures and and
01:41:41so sometimes if a patient has a kidney
01:41:43cancer and a bladder cancer, it may not
01:41:46be a genetic predisposition to that.
01:41:49But perhaps they had an exposure that may
01:41:51have increased the risk of of both and.
01:41:53And so I I do think we we see that a lot.
01:41:57I think we also see it's fairly
01:41:59common to diagnose the second cancer
01:42:01in a patient who has had a cancer,
01:42:03and because we're doing imaging.
01:42:05And and we might find something
01:42:07that wasn't causing any symptoms.
01:42:10You know we're doing a chest scan
01:42:11because someone has a bladder cancer.
01:42:13It shows a thyroid nodule,
01:42:14which leads to an ultrasound
01:42:15which leads to a biopsy,
01:42:17which leads to a diagnosis
01:42:18of papillary thyroid cancer.
01:42:19And that's that's a very very
01:42:21common course of events,
01:42:23and so sometimes these clusters of a
01:42:26couple cancers may just be by chance,
01:42:29or could be from an exposure or
01:42:33or or genetics, but.
01:42:36Hugely important point.
01:42:37Yeah, that we're sort of more biased
01:42:40once we hear it from one thing.
01:42:41Let me go to the last question that I stay.
01:42:45Actually two more, but one is my dad
01:42:47had a tumor in his bladder and had
01:42:49a urostomy can that be hereditary?
01:42:51But instead of the cancer being in
01:42:53my bladder, it was in my left kidney.
01:42:56So in other words,
01:42:57yeah, you got that
01:42:58yeah, great question.
01:43:01So is it possible? Yes, absolutely.
01:43:03It's possible that there could
01:43:05be a genetic syndrome that links
01:43:08those two cancers together.
01:43:10But it's also possible that they're
01:43:12completely unrelated to each other,
01:43:14and both just occurred by chance.
01:43:17So again, I'd I'd have to have more
01:43:19information about ages at the time of
01:43:22diagnosis and other family history,
01:43:23which is why a genetics visit is probably.
01:43:26The best step if you have those questions.
01:43:28Yeah, as Doctor Kennedy pointed out,
01:43:30there are cancers that are in the kidney
01:43:31that are really more like bladder cancers,
01:43:33but they're really different from
01:43:34what we consider kidney cancers.
01:43:36If you have a what we consider a kidney
01:43:37cancer and your father had a bladder cancer,
01:43:40probably not related.
01:43:40I think it's a fair statement,
01:43:42but and then the last thing was can we
01:43:46go through your place to do a test?
01:43:48Yes, absolutely. So the smilow cancer
01:43:51genetics and prevention program.
01:43:53Our main hub is in New Haven,
01:43:56but we also see patients throughout
01:43:58the state of Connecticut at
01:43:59various other hospitals,
01:44:00so we're in Trumbull.
01:44:02We see patients in Waterford we're in
01:44:05Greenwich and we also have an outreach
01:44:07arm up at Saint Francis Hospital in Hartford,
01:44:10so you can if you if you need a a
01:44:14contact information you can actually
01:44:17email smilow cancer genetics.
01:44:20Why nhh.org let us know where you live
01:44:24and we can help find the best clinic
01:44:26for you and we can tell you how to
01:44:29get your doctor to refer you over.
01:44:31It was actually put into
01:44:33the chat that number.
01:44:34Some people aren't great with the web.
01:44:36Is there a phone number
01:44:38and it looks like Renee actually
01:44:40put the website there too,
01:44:42but the phone number is 2032
01:44:45hundred for DNA. Perfect.
01:44:51That's that's very very fitting.
01:44:53Alright, I think I think we're done.
01:45:00Anyone have anything else to add?
01:45:03Well, this has been exceptionally
01:45:05informative to me, so I hope it's been
01:45:07informative to everybody else here.
01:45:09It's great and. By everyone if
01:45:13you have questions you can always.
01:45:14I'm sure there are ways to reach out
01:45:16to any of us and have a great evening.
01:45:20Thank you, I learned a lot too, so thank you.
01:45:23This was wonderful.