Updates in Gynecologic Cancers

April 05, 2021

March 31, 2021

Presentations by: Drs. Elena Ratner and Mitchell Clark, and Johanna D'Addario, PA-C

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00:00I'm Elena Ratner.
00:01I'm the division director.
00:03She went to college, EPL,
00:05and we're so thrilled to be with you tonight.
00:09I'm joined by the most excellent providers,
00:13which I'm so proud to have his
00:16colleagues that the Mitchell Clark,
00:19who is Joanne ecologist who is
00:23practicing currently at Water Ford at
00:26Lawrence Memorial and join the Dario
00:29who is the director and who runs
00:33multiple programs within our practice.
00:35Most notably so that for
00:38early cancer detection.
00:40Call discovery to cure.
00:42And then ********* intimacy
00:44and menopause program,
00:46which is a survivorship program
00:49that we offer for patients with
00:51cancer that has to do specifically
00:54with menopause and with *********.
00:58So we are so excited to be with
01:00you today to share with you
01:03the updates and Joanna Kalaji.
01:05So much has changed in the field of
01:08Joanna Kalaji over the past decade.
01:11You know we no longer treat
01:13the cancer is the same.
01:15You know we no longer treat the women
01:18the same way just because they have
01:21a certain kind of kind of cancer.
01:24We truly now offer a personalized
01:26approach every woman.
01:27Tomorrow get studied and understood
01:30an we truly offer a targeted,
01:33personalized approach.
01:34Not only cancer, but to every patient.
01:37We believe wholeheartedly
01:39in preventative medicine.
01:41Joanna will talk today about the role
01:44of genetics and the role of Previvor ship.
01:48You know, we have struggled over generations
01:51for to find cure for bearing cancer.
01:55Few of ovarian cancer is very complex.
01:58There's a lot of chemotherapy resistance.
02:01There's a lot of reasons why.
02:04Unfortunately,
02:05these cancers recur and hands
02:07with concentrated.
02:08Work for generations on early detection
02:10and so much work and research is
02:13being done in early detection,
02:15but the future of ovarian cancer is
02:17probably not even early detection.
02:19The future,
02:20maybe with the present is just prevention.
02:23Finding the women who are at higher
02:26risk for these cancers and then
02:28preventing cancers in them in the
02:311st place so that early detection
02:33or cancer cure is not even an
02:36entity that this cancers can be
02:39prevented before they even happen.
02:41So that's the Clark today
02:43will share with us updates,
02:45enjoy mycology again.
02:46Kind of concentrating with this
02:48kind of personalized approach
02:49that we offer very much within
02:52Lawrence Memorial and within here
02:54within the Yale Health System.
02:55And then join,
02:56I will talk to you about Providership
02:59and how important it is to find these
03:02women record high risk for these
03:04cancers and how important is to
03:07really have comprehensive approach.
03:08You know,
03:09it is so important to remember that this
03:12genetic mutations do not just affect.
03:14The ovary or the breast that all of
03:16them are intertwined and this is not
03:19just something that affects women.
03:21This is something that affects
03:23women and man for generations and
03:25it is so important that we are
03:27offering this kind of a care to
03:30our patients and their families.
03:31So again,
03:32thank you and welcome and we're so
03:35thrilled to be with you on this Webex.
03:37But really even more so.
03:39We're so thrilled to be part
03:41of your community and to be
03:43providing Joanna Kalaji care.
03:45At Lawrence Memorial Dr Clark.
03:47Yes thank you
03:48so much. I'm just gonna switch over
03:51and share my screen with everyone.
03:56All race. Alright, so thank you so
04:00much Doctor Ratner for the excellent
04:01introduction and thanks everyone
04:03for joining us tonight on this
04:05sort of rainy Wednesday evening.
04:06For those who, I haven't had
04:08a chance to meet you.
04:09My name is Doctor Mitchell Clark.
04:11I'm within the division of dynamic
04:12at Yale and my clinical practice is
04:15focused here at Lawrence and Memorial
04:16and at the Water for Care Center.
04:18And we're going to start tonight
04:20session by talking about updates and
04:22ovarian cancer which Doctor Ratner has
04:24alluded to is very exciting right now.
04:26I don't have any disclosures,
04:27either financial or use of any off
04:29label medication in this talk.
04:31So just some objectives for what I
04:33hope to cover in a quick discussion
04:35on these highlights is talk a little
04:37bit how the proposed origins ovarian
04:39cancer have changed and how this impacts
04:42early prevention and early diagnosis.
04:43Review some of the data on opportunistic
04:46salpingectomy and then risk reducing
04:48surgery for women who are identified
04:50it being a particularly high
04:51risk and then in those women who
04:53do go on to develop a cancer.
04:55How we've increased our
04:57use of new management,
04:58chemotherapy and special interval
04:59surgical techniques for these women
05:01to help manage their advanced disease.
05:03And then probably most exciting of all,
05:05is to discuss some of the
05:07emerging data on maintenance,
05:09treatment,
05:09and so how we can extend the
05:11survival of our survivors of ovarian
05:13cancer for years down the road.
05:16So my practice is primarily focused
05:18here in the water for Care Center.
05:20Like I mentioned before,
05:21we feel full range of gynecological
05:23malignancy's as well.
05:25If complex joint surgical care as
05:27well as patients who are either
05:29thought to have or known to have a
05:31hereditary cancer syndrome which.
05:33Joanna will expand a little
05:35bit on later on this evening.
05:37This data is and is not new for many of you.
05:40Most of you are aware that this is
05:42the second most common gynecological
05:44malignancy that we see in the US,
05:47but it certainly accounts for far
05:49more death and unfortunately in
05:512020 / 21,000 women were diagnosed
05:52with this disease and 13,000 of
05:54them succumb to their illness,
05:56and we've alluded to the problem for decades.
05:59Has been that most of these women
06:01presented a very advanced stage,
06:02and as we would expect from with
06:05all cancers or survival outcomes.
06:07Certainly decrease as stage increases,
06:08but we know now through advances in
06:11molecular testing and things that
06:12will talk about further on that.
06:14These are not just all the same
06:17ovarian cancer and the site is very
06:19busy and there's no quiz at the end,
06:22but just to highlight the real
06:24heterogeneous grouping of histologic
06:26subtypes and how important it is
06:27that we expand our knowledge of how
06:30each of these relate to diagnosis
06:32into treatment and to survivorship.
06:34This is a picture taken out of
06:36a book that you know many of us
06:39have probably seen in our
06:40training, highlighting the survivorship
06:42and lifetime experience of women with
06:44ovarian cancer that really shows a sort
06:47of antiquated experience that many of
06:48us have been dealing with for years,
06:50which is survival measured in
06:52many months and not many years.
06:54And I hope we can circle back to this
06:56figure at the end of the talk and
06:58show how these advances in ovarian
07:00cancer have really LED us to believe
07:03that we're going to pull this graph.
07:05From side to side and really expand the
07:08Survivor ship time and disease free time
07:10that our patients are able to experience.
07:12So what came first?
07:13The chicken or the egg?
07:15And you know where did this cancer come from?
07:18Some of you may be aware of the data
07:20that is emerging to suggest that maybe
07:22the most common types of ovarian cancer
07:25actually started in the tube for years.
07:27We thought that it was this obligatory
07:29rupture on the surface of the ring
07:31that was causing these mutations,
07:33and cancer would go on to develop.
07:35But now there's some really exciting.
07:37Research and and special pathology
07:39techniques were identifying these lesions
07:41at a very early stage or what is called
07:43the stick lesion or the precursor lesion,
07:46and through this work and
07:47some very exciting science,
07:49we actually think that the most likely
07:51mechanism is that these these cancers
07:53probably start in the tube and then
07:55migrate into the peritoneal cavity
07:57and spread in the in the way that
08:00we know ovarian cancer to behave,
08:02and so that brings up the opportunity of a
08:05salpingectomy for our women who are average.
08:07Age, risk and what is an
08:09opportunistic salpingectomy?
08:10When are these opportunities?
08:11If you're telling me the cancer
08:13is starting in the tube,
08:15well,
08:15let's take them out so this can
08:16be at times when women are having
08:19hysterectomy for benign indications.
08:21Women who are undergoing cesarean section,
08:22desire surgical sterilization or
08:24perhaps women who are searching,
08:25searching for surgical sterilization.
08:27Outside of pregnancy.
08:28You know,
08:28I hear a lot of providers said to me,
08:31you know,
08:32I've been doing one technique for years.
08:34I do the Pomeroy or the modified
08:36Pomeroy very happy with it.
08:38I'm very comfortable.
08:39Is the data strong and what is the benefit?
08:42And this just highlights some of the
08:44exciting research that's come out of
08:46some of the cancer registry showing
08:48a 35% risk reduction for death from
08:50ovarian cancer in women who underwent
08:51an opportunistic self inject to me.
08:53I hear a lot of people say.
08:55Also, you know, I'm a little worried.
08:58At the time of C-section.
08:59Those tubes are really engorged
09:01or I'm worried about blood loss,
09:03but Jessica McAlpine,
09:03who was a fellow here at Yale a
09:06number of years ago and have gone
09:08on to Vancouver and done amazing
09:10research and work out there.
09:12Show that in her series there was
09:14no increase, blood transfusion,
09:15hospital,
09:16length of admission was the same
09:17and no re emission rates.
09:19Being higher for those who
09:21underwent this procedure and really
09:22only added to 10 to 15 minutes of
09:25additional surgical time, so you know
09:26that's our average age risk women,
09:28but I've Joanne is going to talk about later.
09:31What do we do for patients who are known
09:34to harbor a mutation in one of these genes
09:37that significantly increases their risk?
09:39And we've traditionally been doing
09:41risk reducing bilateral salpingo for
09:43ectomy when women have made that
09:45decision after information is shared,
09:47decision making with their provider.
09:49But there are complications related to
09:51quality of life from surgical menopause.
09:53These are important decisions
09:54that women make,
09:56balancing their quality of life
09:58against the risk of cancer and so.
10:00Two separate research groups have now
10:02collaborated to explore the idea of well,
10:04if this is in the tube,
10:06why not just take out the two?
10:09And so I want to caution you.
10:11This is still an ongoing clinical trial,
10:13but something I wanted to highlight
10:15as emerging evidence that's
10:16hopefully coming down the pipeline.
10:18The Tubo whiffed study,
10:19which is a combination of a an American
10:22and European initiative that looks at
10:24doing just the tube and delaying new
10:26for ectomy for delaying that time again.
10:28We don't have the data yet.
10:30For this,
10:31and we're hoping to see what
10:32emerges from this trial,
10:33but just to highlight the fact
10:35that we're really are focused on
10:37trying to prevent this ovarian
10:38cancer before it even happens,
10:40and finding ways that we can do that,
10:42that balance of quality of life and
10:44individual choices for women when they're
10:46trying to decide what to do for themselves.
10:48Unfortunately,
10:49a number of women will go on to
10:51develop an advanced ovarian cancer,
10:53and I'm sure like many of you and your
10:55guy knock rotation as resident you
10:57were involved in these long complex
11:00operations with lots of disease and we
11:02are really complex surgical debulking
11:04because for decades our knowledge
11:06was that you know a big operation.
11:08Removing all the visible cancer as
11:10possible gives the best outcome to women,
11:12but I'm sure you also saw a lot of
11:15patients experience more bitteti summer.
11:17Fortunately,
11:17mortality and high complication
11:19rates for those.
11:20Who are universally treated with the
11:21same approach so universally taken
11:23to the OR without consideration
11:25of individual life factors.
11:26And so there have been a number of
11:28trials exploring the use of how
11:30we give some chemotherapy.
11:31First, let's shrink this cancer down.
11:33Let's try to have an operation that
11:35maybe is a little less radical,
11:37but can still provide the same
11:39Uncle logic outcome for women.
11:41And this is just one of those
11:43trials that I wanted to highlight
11:45which is the chorus trial.
11:47These folks randomized advanced age
11:48ovarian cancer to undergo either.
11:50Upfront surgery followed by chemotherapy
11:52or some chemotherapy first followed by
11:54surgery followed by more chemotherapy
11:57and therewithal show essentially
11:58the same thing that both arms of
12:00this study showed equal survival,
12:02both overall and progression free
12:04survival and we've now gone on to
12:07further analyze and try to identify
12:09for each individual woman who's
12:11best served by a primary surgery,
12:13who's best served by neoadjuvant
12:15chemotherapy and really trying to
12:17make sure that we're picking the
12:19right thing for the right patient.
12:21And not treating this as just one lump
12:24category of disease and with that has come
12:26the adoption of minimally invasive surgery.
12:29For ovarian cancer,
12:30you know, ten years ago,
12:31this is something we would really
12:33have not even considered or thought about.
12:36But as we're treating more and more
12:38women with neoadjuvant chemotherapy,
12:40we're seeing more and more women who
12:42may be good candidates to undergo
12:44a minimally invasive approach.
12:46So what is the role of robotic surgery?
12:48Minimally invasive surgery?
12:49In this disease, you know?
12:51For women who are not able to
12:53undergo that primary debulking
12:55surgery did individualy factors,
12:56there may be an opportunity to
12:58offer them a surgery with all the
13:00benefits of laparoscopy while still
13:02maintaining the same oncologic outcomes.
13:04And so we're very excited to see the
13:07development of randomized control trials
13:09that are going to answer this question.
13:12These are ongoing,
13:12but until then we continue to look for
13:15patients who are excellent candidates who
13:17may be able to benefit from a minimally
13:20invasive approach when carefully.
13:22Select it.
13:24One additional exciting advance
13:25in the way we do these interval
13:27surgeries is the incorporation of
13:29what is called heated or hyperthermic
13:31intraperitoneal chemotherapy.
13:32For those of you who've taken care
13:35of patients with appendix feel
13:37cancer with some of the other
13:39GI cancers you may be aware of.
13:41This technique for those diseases,
13:43but we've seen randomized evidence
13:44to show that in women who are
13:47carefully selected and offered
13:48this as part of their treatment,
13:50they actually experienced an improvement
13:52in their survival as well again.
13:54All about making the right
13:56selection for the right patient,
13:58taking into account all those
14:00individual life factors.
14:01This is not a one or one solution for
14:04every woman type of disease anymore.
14:07And just to finish off of what I think
14:10is probably some of the more exciting
14:13evidence and will sort of lupus
14:15into joann's discussion very nicely
14:17is really the role of maintenance
14:19therapy and how our understanding of
14:21the biology of the tumor is critical
14:24in assessing individualized treatment.
14:26Patients complete their chemotherapy.
14:27We know that.
14:28Unfortunately,
14:28most of our patients with advanced stage
14:31disease will experience a recurrence
14:33at some point in their cancer journey.
14:35So how can we extend that time between
14:38recurrences while maintaining excellent?
14:40Quality of life.
14:41I'm not going to get too much into
14:44the field of molecular biology here,
14:46but there are some very exciting
14:49studies showing that almost half of
14:51ovarian cancers are deficient in
14:53mechanisms that allow for DNA repair
14:56and without taking us all back to our
14:58undergraduate molecular biology course.
15:00Really.
15:00To just summarize that we're
15:02really exploiting the inherent
15:04problems with these cancer cells
15:06and turning them off themselves,
15:07and so through some very
15:09exciting preclinical and.
15:11Clinical trials we seen that
15:12these class of medications,
15:14called PARP inhibitors,
15:15which are an oral drug taken for two
15:18to three years after chemotherapy.
15:19I've had excellent results in
15:21allowing patients to experience
15:22a prolonged survival solo,
15:24one which was just published a
15:26couple of years ago with probably
15:28the most exciting of these trials.
15:30These were women exclusively with
15:32the bracket one and bracket two
15:35mutation either in their tumor or
15:37in their all of their country,
15:39or all their cells, or both.
15:41The germ line and when given for two
15:43years after they completed their treatment,
15:46they had significantly longer
15:48progression free survival than those
15:50women who went on to take placebo.
15:52And this is hot off the press from
15:54the Fgo meeting about 10 days ago.
15:57Really thrilling results to see the
15:59five year updates of this trial,
16:02and these are just numbers we never
16:04dreamed of seeing an ovarian cancer with
16:06patients were randomized to elaborate,
16:08having a median progression
16:10free survival of almost.
16:11Five years and you know,
16:13if we just think about the women,
16:15we've carefully over the
16:17years with ovarian cancer,
16:18to imagine telling someone after
16:20their initial treatment to expect a
16:22five year progression free survival.
16:23Let's just, you know,
16:25really,
16:25thrilling stuff that we could
16:27have never imagined in the past.
16:29There's still a role for these
16:30types of medications and women
16:32who are not bracket carriers.
16:34Which is why we are very diligent
16:36about testing tumors and understanding
16:38the unique characteristics of
16:39every woman's of varying cancer.
16:41Earth data to support the use of these
16:44drugs in all comers with ovarian cancer,
16:46but the strength of those
16:47recommendations in the data is
16:49certainly less for those women who
16:51don't have these inherent mutations
16:52or changes in their tumor DNA.
16:54So we take the time to really explore
16:56that so we can offer women as much
16:59education and data so they can make
17:01a decision about how they want to,
17:03how they want to manage their care.
17:07This circle back to that figure that
17:09we talked about in the beginning and
17:11to just highlight some of the things
17:13we've talked about tonight and how
17:15we're trying to pull this graph from
17:18side to side and extend the survival.
17:20We hope through perhaps one day
17:22being able to do self inject
17:23to me or to continue doing BS.
17:26So now we're able to prevent
17:27ovarian cancer from developing,
17:29were able to improve the treatment of
17:31women when they are diagnosed with
17:32their disease. Anthru PARP inhibition.
17:34We hope to extend that survival for
17:37women for many many years to come.
17:39And so there's still a lot of
17:41exciting work going on,
17:42and I hope we can go back to you next
17:45year with an update that just shows
17:47that we're measuring the survival.
17:49And many many many, many years.
17:51So with that I thank you so much
17:53for listening and will hand things
17:55over to Joanna. Any questions.
17:57Right now we can take them.
17:59Otherwise we're going to have
18:00a great Q&A session at
18:02the end.
18:07I don't think we have any questions to
18:09Joanna. Maybe you want to lead us in sure.
18:13You're my slides here.
18:15Thank you so much, Doctor Clark for the
18:17opportunity and for inviting me to join
18:20you guys tonight and Doctor Ratner.
18:22Thank you for the nice opening.
18:24Welcome, and so I will certainly
18:26try to keep my talk to 15 minutes.
18:28But if there are any questions
18:30at all during the presentation,
18:32there is a Q&A.
18:34Section at the bottom of your screen
18:36and you can type in a question
18:38and we will get to it either
18:40during the presentation or after.
18:42So I wanted to talk a little bit
18:44more about genetics and Joanne
18:46Oncology and my name is Joanna.
18:48I am a physician assistant
18:49trained at Quinnipiac University.
18:50I graduated in 2008 and I've
18:52been part of the practice at
18:54Yale for about three years now,
18:56so I'm thrilled to share
18:57some information with you.
18:58I have no disclosures tonight.
19:01So we're learning more and more about the
19:04genetics of gynaecologic cancers and so.
19:07Of course,
19:07for the for probably about
19:0920 to 25 years now.
19:11We've known about the bracket
19:13one and bracket two genes,
19:15but we're finding out about the
19:17additional genes that are implicated
19:19in gynaecologic cancers, pal B2,
19:21brip one, the RAD 51 jeans,
19:23and some other ones.
19:25So these mostly lead to increased
19:27risk of breast, ovarian,
19:29fallopian tube, and peritoneal cancer,
19:31as well as possibly pancreatic.
19:32And prostate cancer.
19:34And in bracket two specifically.
19:36A risk of Melanoma.
19:37You may know about the Lynch syndrome
19:40genes or the DNA mismatch repair genes
19:44that can lead to multiple cancers.
19:47We often think about the GI cancers
19:49like bowel or colorectal cancers,
19:51but also endometrial Arian cancers.
19:54Some of the less common genetic
19:56syndromes that we learn about our
19:58leaf from many syndrome or TP5.
20:00The three mutations Cowden syndrome
20:02or PTN and Pronunciator syndrome,
20:04which is the STK 11 or LKB one jeans.
20:08So these can have multiple different
20:10types of cancer and even benign tumors
20:14that affect women with put Seager syndrome.
20:17When we think about the inherited
20:19breast and ovarian cancer syndromes,
20:21we think about about 15 to 20% of
20:23ovarian cancers being caused by
20:25a BRCA or or similar mutation and
20:27about the same for breast cancer.
20:29One of the differences is that
20:31breast cancer also can have more
20:33familial clustering where you can
20:35see these families with multiple
20:36cases of breast cancer but may not
20:39have a specific gene identified,
20:40and we can also see that in
20:42ovarian cancer as well,
20:44we do see women who have a couple different
20:46family members with ovarian cancer.
20:49But no gene identified yet.
20:51So there's probably still more down the
20:54road that we will learn about with the time.
20:57The risks this is probably
20:59a little outdated now.
21:00Now this is from 2018,
21:01but we are, you know,
21:03learning more each year.
21:04The risk with BRCA one and BRCA two
21:07in regards to ovarian cancers is
21:09about 40 to 50% risk but lots of
21:11different numbers that we see for
21:13Braca one anfar bracket two a
21:15little bit lower risk and also a
21:17little bit later in life than the
21:19Bracco one risk for ovarian cancer.
21:26I'm actually going to skip this slide
21:28so it's a really important to test
21:31for test for the BRCA mutations in are
21:34any woman with an ovarian cancers,
21:36especially high grade serous ovarian cancer.
21:38But really now the recommendation is any
21:41ovarian cancer type should have genetic
21:43counseling and offer genetic testing not
21:45only because it can help the patients
21:48in regards to knowing their prognosis.
21:50Knowing their decisions,
21:51for example as Doctor Clark mentioned the.
21:53Carpet hitters and also being able to
21:55put the patient into long term remission
21:58and at that point we sometimes now are
22:00preventing other cancers that we do
22:02have ovarian cancer survivors who are
22:04doing well from their disease and are
22:06now having a risk reducing mastectomy
22:08to prevent breast cancer as well.
22:10Of course,
22:10it's important for the relatives to
22:12know as well so that if there is a
22:15mutation in the patient's DNA then
22:17they can have cascade testing in
22:19the rest of the family members and
22:20who can also have risk reducing
22:22or prevention strategies.
22:26So again, the most common thing that we
22:29like to talk about is hereditary breast,
22:31ovarian and pancreatic cancer.
22:33Specifically the BRCA one
22:35and two genetic mutations.
22:37More common than we used to think,
22:39so depending on the source,
22:41we're now learning that there
22:43is a bracket mutation present in
22:45about 1 in 200 people in general,
22:47and in the Ashkenazi Jewish
22:49population about one in 20 people
22:51may carry a mutation in bracket
22:53one or bracket two, so really,
22:55really not as rare as we used to think.
22:58Recommendation again from the
22:59Cancer Network and this Society of
23:02Joanne Oncology is for universal
23:04genetic counseling and testing
23:05for anyone with ovarian cancer.
23:07Another important thing to remember
23:09is that they are not the same,
23:10so Braca one is not treated or
23:12or prevention is not the same
23:14as the bracket two patients.
23:15So we have to take that into consideration.
23:20Lynch syndrome is the same.
23:21There are different genes,
23:22and they're not all the same,
23:24so we need to make sure that
23:26we're not treating each Lynch
23:27syndrome patient equally.
23:28And I'll show you a nice sample of that.
23:32On the next slide,
23:34genetic testing is recommended
23:35for women with endometrial cancer
23:37or colorectal cancer as well,
23:39men and remote colorectal cancer
23:41who have evidence of what's called
23:43microsatellite instability or
23:44a loss of DNA mismatch repair
23:46proteins on immunohistochemistry.
23:48So this is where now every colon cancer,
23:51an every endometrial cancer is getting.
23:53This special testing the microsatellite,
23:55testing the IHC an if it's
23:58identified that they have an issue.
24:00They will then go for genetic
24:02testing and counseling to see if
24:05they carry a germ line lynched.
24:07Premutation so the the National
24:11Comprehensive Cancer Network has
24:12really nice tables and guidelines
24:14for the prevention of cancer and
24:16the risks of cancer in both the BRCA
24:19mutations and the other mutations
24:20as well for HBO See syndrome,
24:22but also for Lynch syndrome.
24:24So I'm just giving you one example
24:27of the MLH,
24:28one which is the one of the more
24:30common Lynch syndrome genes and it
24:32gives you a specific cancer risks,
24:35or at least ranges of risk compared
24:37to general population for each
24:39of the associated cancers.
24:40And what's really important to know
24:42is that MLH one has a higher risk
24:45of many cancers than for example,
24:47PMS two.
24:48So it's not just Lynch syndrome
24:50is 1 size fits all.
24:55So what are the guidelines for
24:56identifying who should be screened
24:58for genetic cancer syndromes?
25:00Well, I'm just going to go over
25:02briefly in the next 10 minutes or so.
25:05The guidelines from ACOG,
25:07the National Comprehensive
25:08Cancer Network, the USPS TF,
25:10and Society of Duane Oncology.
25:14In a committee opinion piece from 2011,
25:17there were just very general guidelines
25:19that women should have family
25:21history evaluation as a screening
25:23tool should be reviewed and updated
25:26regularly and when appropriate,
25:28further evaluation should be considered
25:30and referral to genetics as needed.
25:32That was updated with a lot
25:35more information in 2019.
25:36So this is kind of talking about you
25:39know every patient in your practice.
25:42In general, Obi Wan should have
25:45a hereditary risk assessment.
25:46Taking a good family history and
25:49if there's suggested that there's
25:51an increased risk of a hereditary
25:53syndrome referring to a specialist,
25:55or if you have the expertise in genetics,
25:58then or someone in your practice.
26:00For example,
26:01a practice nurse can give that counseling
26:03and make an educated decision about
26:06genetic testing for the patient
26:08or the appropriate family member.
26:12We are now doing more multigene testing,
26:14so this is panel testing as opposed to
26:16just the Braca one and bracket two test.
26:19It's much more affordable than
26:20it used to be and the tests are
26:22better than they used to be,
26:24so we also recommend that people
26:26who had genetic testing before
26:27about 2012 be offered updated
26:29panel testing to make sure that we
26:31didn't miss anything back then.
26:35Another guideline talks about the importance
26:37of pre test and post test counseling,
26:39so I know these are busy slides,
26:41but talking about you know what it
26:43means to have genetic testing what
26:45the result might be and what it might
26:48mean for their family for themselves
26:50for their medical insurance and life
26:52insurance and how to communicate those
26:54results to the patient and counsel
26:56them after the test results are back.
27:02If there is a clinically significant
27:04mutation, patients should really be
27:05encouraged to share the results with
27:07their family members and recommend
27:08that the family members also be tested
27:10and that can be really hard to manage.
27:12The question is, am I then as the provider
27:15responsible for the family members?
27:16And that's sometimes where a
27:18genetic counselor can really help
27:19you by drafting a letter,
27:20the patient can give the letter to
27:22their family members and they can
27:24help share the information for how
27:26everybody in the family can get tested.
27:30The USPS TF recommendations were
27:32updated about a year and a half ago,
27:35and this was in 2019 and one of
27:37the biggest changes to this was
27:39when collecting a family history
27:41to also collect information about
27:43any Ashkenazi Jewish ancestry.
27:45So really, that should be one of
27:47your questions on the screening
27:49for family history.
27:50Do you have any family history of cancer?
27:53What types of cancer, what relatives? And?
27:56Is there any Jewish ancestry in your family?
27:59So that's one of the biggest.
28:01Updates in the guidelines.
28:04Again, the is talking about
28:06integrating services,
28:07individualizing your questions,
28:08and plan for genetic testing for
28:11your patients to optimize the
28:13benefit and minimize the harm.
28:17So that the USPS TF report was published
28:21in JAMA about a year and a half ago.
28:24Again, talking about identifying
28:26appropriate candidates for genetic testing
28:28and then what type of tests to order.
28:31So there's lots of different
28:33steps in the process about what
28:35are the harms of asking?
28:37What are the harms of testing?
28:40What are the harms of
28:42intervention after we test?
28:47I do see a question in the Q&A
28:49that will try to get to shortly.
28:51So the USPSTF recommendation does give
28:54a B recommendation that primary care.
28:56Clinicians, including Obi Wans,
28:58assess women with a personal or
29:00family history of breast, ovarian,
29:02tubal or peritoneal cancers,
29:04who have any ancestry associated with
29:06BRCA mutations with an appropriate risk
29:09tool and they do give some options
29:11for different tools to use and if
29:14there's a positive result on the tool,
29:17they should receive genetic
29:19counseling and potentially genetic
29:21testing if they're interested.
29:23They do not recommend.
29:26Counseling for women whose ancestry is
29:28not associated with a potential mutation.
29:31So we're not sending everybody
29:33every woman for genetic testing.
29:38One of the examples is a seven
29:41question family history screening,
29:43others included Ontario
29:44Family History Assessment,
29:45Manchester Scoring System,
29:47the referral screening tool,
29:48a pedigree assessment tool
29:50and the tire acoustic model,
29:52which is good for breast cancer risk.
29:55So these are just short screening
29:57models that can be used in your
29:59practice for regular annual visits.
30:03Shifting gears to the SGO,
30:04SGO again recommends genetic
30:06counseling and testing for women who
30:08are at risk of having a hereditary
30:10breast and ovarian cancer syndrome.
30:12They are recommending more
30:13and more now to again,
30:15have somebody help you with that,
30:17or as a primary provider to have
30:19the expertise and I'll show you
30:21some ways that we can gain that
30:23expertise to provide genetic
30:24counseling for our patients.
30:26It is always important to have experts
30:29available after tests to help you know,
30:31interpret the tests and recommend
30:33the treatment plan.
30:35Important to have an interdisciplinary
30:36team and I'll show you who the
30:38team members might be for somebody
30:39who has a hereditary cancer risk.
30:45This talks about their women's personal
30:47cancer history and the family cancer
30:50history and who should be offered
30:52genetic counseling and testing.
30:54So there's anybody with a high grade ovarian
30:57cancer of breast cancer early in life,
30:59pre menopausal women who have a limit that
31:02family history or family history is unknown.
31:05Women who have a pancreatic cancer,
31:07family history or prostate cancer.
31:09Women who have a triple
31:11negative breast cancer.
31:13Women who have breast cancer with
31:15Ashkenazi Jewish ancestry, etc.
31:19And then there may also be situations
31:21where you'd want to refer for
31:23genetic counseling even if you
31:25don't know the family history.
31:27So for example, if someone
31:28has very few female relatives,
31:30many relatives had hysterectomy at
31:32a young age for unknown reasons,
31:34or there's adoption in the lineages and
31:36you may not know also for Lynch syndrome.
31:39Again, mutations anyone with an
31:41endometrial or colorectal cancer
31:42has the mismatch repair genes
31:44or microsatellite instability.
31:45Or again, depending on the
31:47family history of colorectal.
31:49Are gynecological cancers?
31:54If you don't have access
31:56to the NCC and guidelines,
31:58I would certainly encourage you to sign up.
32:01It's a free membership for NCC N.
32:04To access the guidelines for prevention and
32:07cancer risk reduction an A couple years ago.
32:10Now, this was changed from breast
32:12and ovarian cancer, now to breast,
32:14ovarian and pancreatic cancer syndrome,
32:16so pancreatic cancer is becoming more
32:18recognized as part of this cancer history
32:21syndrome syndrome and pancreatic cancer.
32:24Is now an indication for genetic counseling
32:26and testing as well as any first degree
32:28relative of a pancreatic cancer patient.
32:30Should have genetic testing if
32:33that person is no longer living.
32:36So, NCCN recommends that pretest
32:38counseling be done prior to testing.
32:40Consideration of the most appropriate
32:42test to order and then post test
32:45counseling when the results are disclosed.
32:47So then anybody who again has that
32:50experience and expertise in cancer
32:53genetics should be involved at each stage.
32:56And so there's some good algorithms
32:58to help with how we do this,
33:00how we help the family and what the
33:03outcomes might mean for our patients.
33:06The NCCN also has some really nice
33:08tables about what the cancer risks
33:10are and what the recommendations are,
33:12so this is just one page of the guidelines,
33:15but there are actually 3 pages that
33:17include each of the different mutations
33:20that your patient might carry.
33:22And of course,
33:23they're not all treated the same.
33:25So for example,
33:26we've seen patients in our office who
33:28understood or heard that that he or
33:30she carries a mutation in the bracket
33:32gene and they come to us saying,
33:34I have the Angelina Jolie gene,
33:36and then we find out that on their
33:38genetic testing they actually carry brip,
33:41one which has a much lower risk and is
33:43managed very differently than brocco,
33:45so it's important for us.
33:46We like to see the patients genetic
33:49testing results with our very
33:50own eyes before we start to make
33:52management recommendations.
33:53So just to kind of move on here,
33:56this is what's really
33:57important for our patients.
33:59It is a long process.
34:00We need to 1st identify the risk,
34:02give some counseling,
34:03identify who the best person in the
34:05family would be for genetic testing.
34:07Have that person tested.
34:09Do the post test counseling.
34:10So what does it mean?
34:12If it's a positive or negative test result,
34:14offer testing for the rest
34:16of the family members.
34:17That's called cascade testing.
34:19Provide emotional support and that
34:20really is part of the entire process,
34:22not just a single step in the process.
34:25We have to emotionally support our
34:27patients with this complex disc.
34:28Asian making referrer as
34:30appropriate for breast surveillance
34:32on gynecological surveillance,
34:34pancreatic surveillance skin exams,
34:36all the different referrals
34:39that are necessary.
34:41Support them in fertility decisions
34:44about their children if they are young.
34:48And then provide the cancer surveillance
34:51and cancer prevention if we can.
34:53So it is a lot of work.
34:55There are a lot of questions
34:57that we can ask
34:58ourselves. Do I do I have time to
35:00collect a full family pedigree?
35:02Do I remember how to do that?
35:04Does the patient know their family history
35:06or do we need to go back and gather more
35:09information from other family members?
35:11Do I? How do I know what test to order?
35:13Does my patient, you know,
35:15have the emotional readiness for the testing?
35:17Will they be OK with the result?
35:19Do they want to be tested or do they
35:21want not want to know their genetics?
35:24Should I recommend or?
35:25If my patient asks about things like 23
35:28andme or the direct to consumer testing,
35:30do I know how to help him
35:32or her interpret that test?
35:35Who is the right person to be test tested?
35:37Am I ordering the right test?
35:39Am I ordering from the right company?
35:41What is the test mean?
35:42You know this is not just
35:44positive or negative anymore.
35:45It's now likely pathogenic,
35:46pathogenic, likely benign or benign,
35:48and then in the middle there's
35:50this variant where we know
35:51there's a change in the gene,
35:53but we don't know if it's
35:55necessarily cancer causing.
35:57How do we proceed with the family members?
35:59Do I have to follow up all the
36:01family members testing and how well
36:03does it affect my patient as far
36:05as insurability and general health?
36:08So there's a lot of things that we may
36:10not know how to help our patient with,
36:12and we need to know where to
36:14refer them to if needed.
36:15This is what I was talking about
36:17with a different test results
36:18that can occur on testing.
36:22And if you've ever come into, you know,
36:25finding a test result or coming into a
36:27conundrum where you didn't know the answer.
36:30You're not alone, and there's actually
36:31a series of articles from some of our
36:34Yale genetic counseling colleagues.
36:36Karina Byerly, who's one
36:37of our genetic counselors?
36:38Danielle Bonadies,
36:39Danielle Campfield was her maiden name,
36:41who is one of our genetic counselors
36:43who's no longer at Yale but has
36:45done some great work and talking
36:47about the errors that can happen.
36:49The wrong test is ordered.
36:51The test result is misinterpreted,
36:53or there's not enough patients.
36:55Follow up so it happens.
36:56It's not common.
36:57It's not uncommon for the test
36:59to be interpreted incorrectly,
37:01and that's where our genetic counseling
37:04colleagues can really help us.
37:07It certainly takes a village
37:09to support these patients,
37:10so whether your patient has a
37:12mutation or has a family history.
37:14First of all, she's probably seen cancer,
37:17and she's probably experienced
37:18a loved one who's been diagnosed
37:20and treated for cancer,
37:22and there's trauma involved in that.
37:24The patient probably has a lot of
37:26questions and concerns about her family,
37:28her children,
37:29what it means for her health,
37:31and so it takes a lot of people to
37:34really help support this patient in
37:36making sure she gets the best care.
37:41A smile has some great resources.
37:43The cancer genetics and Prevention program,
37:46which is available also by telemedicine.
37:48These days there's a lot of resources
37:50from ACOG that are available online.
37:53Jackson laboratory up at UConn has some
37:56modules that I'll show you shortly
37:58SGO has some information and there is
38:01a fee if you're really interested.
38:03A certificate program that's online in
38:06clinical genetics and genomics and this
38:08program is actually for physicians or nurses,
38:10or. PSA PRNS who are interested in learning
38:13more about genetics and want to, you know,
38:16help advance their care, and it's all.
38:19It's a one year online program.
38:22The Jackson Laboratory genetics modules
38:24are great because they're 15 minutes
38:26case based and they do give you CME
38:29credits so those are available at
38:31Jackson Lab which is part of UConn and
38:33there are 11 cases in that in those
38:36modules and the Society of Joanna
38:38Kalaji also has a genetics tool kit
38:40that has seven case based modules
38:43that's available for providers on line.
38:47Yale's cancer Genetics and Prevention
38:48program is at the Saint Rayfield
38:51campus in New Haven. It's Co.
38:53Directed by Doctor Hofstetter and Doctor
38:55Your who managed Breast and GI Oncology,
38:57Doctor Bale is the genetic scientific
38:59director and there are many great
39:01genetic counselors available to
39:03answer any questions that we have.
39:05And of course, Dr Ratner and
39:07myself are there to support women.
39:09And Doctor Ferrell helps with
39:12pancreatic cancer surveillance.
39:14Genetics can be referd through
39:16epic or by calling 201 DNA.
39:21And with that I will stop and
39:22take questions or we can move
39:24on to the next presentation.
39:25Please feel free to contact
39:26us anytime you can email.
39:28Call me and we're happy to
39:29help see patients or help with
39:31answering any questions or getting
39:32you to the right people.
39:33So thank you so much I will hand it
39:35back over to Doctor Clark and we
39:37can take questions if we need to.
39:41Thanks Joanna. I think you know,
39:42I think this is a great question by Kim.
39:45Thanks Kim for for sharing your personal
39:47experience with the meeting and maybe
39:49I'll just read out Kim's comments,
39:51slash question and maybe you
39:53can give us a little bit of
39:55guidance from your perspective.
39:56Joanna so Kim writes just to say
39:58that it was recommended to me.
40:01When I received a breast cancer
40:03diagnosis in prior to genetic testing
40:04to go ahead and secure life insurance,
40:07if a mutation is identified,
40:08it can make it difficult and
40:10or impossible to get coverage.
40:11I thought this was a great idea and
40:15share that with my patients now.
40:17So what's your experience or or is this
40:20a question that you get from patients
40:23who come through the Genics program
40:25that you oversee June? We absolutely do,
40:28and so if you haven't learned about it,
40:31there's something called the genetic
40:33Information Nondiscrimination Act or Gina
40:36and Gina prevents people with a genetic
40:39predisposition to cancer from being.
40:41Denied a job or health insurance.
40:43Unfortunately Gina does not protect people
40:45from being denied life insurance coverage,
40:48so life insurance certainly is
40:50something to consider before
40:52people undergo genetic testing.
40:53If that's important to you and the
40:56genetic counselors are pretty good
40:58at talking about that as well.
41:01But for health insurance and for employment,
41:03there is some legal protection from
41:07discrimination for people who have.
41:09A predisposition to cancer
41:11re thank you. Alright, so we'll just move
41:13on to our final session for the evening.
41:16We're going to switch gears a little
41:19bit away from ovarian cancer and
41:21genetics and how that relates to
41:23gynecological cancers and talk a
41:25little bit about cervical cancer,
41:27both prevention and detection.
41:28I think we have a great group tonight
41:31that ranges from gynecologist to
41:33those who do a lot more primary care,
41:36so I thought this would be a relevant.
41:39Discussion to talk a little bit of
41:42the updates from the SCCP will talk
41:44a little bit about HPV vaccination
41:47and understanding the role of HPV,
41:49and so I'm just going to switch
41:53over my slides here. OK. Great.
41:57And it's the same me talking.
42:01We're just going to shuffle over
42:04to physical cancer prevention.
42:06And.
42:08So we're going to review a little
42:10bit The Who global strategy
42:11to eliminate cervical cancer,
42:13which has been recently put forward and
42:15discussed heavily at the recent fgo meeting.
42:17As this is a priority for The Who,
42:20but then loop that back to how does that
42:22affect us here at home in Connecticut?
42:25In the United States,
42:26will talk quite extensively about
42:28the data on HPV vaccination as well
42:30as the indications and how that has
42:32evolved overtime and then learn to
42:34apply technique for how we can improve
42:36our vaccination rates here at home.
42:38Specifically related to what?
42:40We're kind of coining the catch up cohort,
42:42and then we'll segue into a little bit
42:45of a discussion on the updated 2019
42:47AFC CP guidelines and how the newly
42:50developed app that can be downloaded
42:52from the Android or iTunes Store.
42:55It can really help you guide your
42:57decision making and provide women the
43:00most individualized risk assessment
43:01when trying to decide how to manage
43:04abnormal cytology or biopsy results.
43:06I don't have any financial disclosures
43:08were not talking about anything off label,
43:11but I do want to just acknowledge
43:13and thank Merck for providing some
43:15of the infographics and informatics
43:17on HPV data as it relates to the
43:20cervical and head and neck cancer.
43:23We're going to talk extensively about today.
43:26So again,
43:27I think this is all very
43:29familiar information,
43:30but worthwhile to remember that cervical
43:32cancer is really a global burden.
43:34It's the fourth most common cause
43:36of cancer in women worldwide,
43:38and in 2018,
43:39/ 1/2 A million women were diagnosed with
43:42this disease and over 300,000 of women died.
43:45Almost all cervical cancers are
43:47related to an HPV infection,
43:49and what we see here on the top is a
43:52figure that highlights the incidence
43:54of cervical cancer worldwide,
43:56where we see a disproportionate burden.
43:59African countries as well as
44:01certain South American countries.
44:02And then when we juxtapose
44:04that against the bottom image,
44:06showing the implementation of
44:08publicly funded HPV vaccine programs,
44:10we really see how HPV vaccination
44:12and prevention through primary
44:14prevention methods have been effective.
44:16And it's just unfortunately not
44:17available in the region of the world
44:20where this disease is prevalent,
44:21as it is here, the devil would show
44:23is really taking a multi prong public
44:25health approach to try to reduce the
44:28burden of physical cancer worldwide.
44:30And the best way to do that
44:32is through prevention.
44:33Primary prevention through
44:34vaccination efforts,
44:34and I'm not going to all of the
44:37details of their of their plan.
44:39But what I do want to highlight is
44:41that you know as much as we talk
44:44about this as a global problem.
44:46We really have an opportunity for
44:49improvement closer to home and
44:51this is the CDC data on vaccination
44:54rates as of 2018 for HPV vaccine,
44:56and we see that for girls age 13 to
44:5917 and boys age 13 to 17 are rates of
45:03vaccination were approximately 50%.
45:06That's pretty low when we compare
45:08that to other vaccines given in
45:11the same age category.
45:12So we think Mcninja cockle,
45:15which has a 90 to 95% vaccination uptake.
45:18Great,
45:18there really is an opportunity to
45:20improve here and I hope at the end
45:22of this will have highlighted some
45:23techniques in ways that you can
45:25improve that in your own practice.
45:28Just want to go through sort of the
45:30impact of HPV and again I want to
45:33thank Mark for providing some of
45:35this information or these graphics
45:37which really depict the burden
45:39that HPV has on the lower genital
45:41tract and head and neck disease.
45:44They are over 14 million new HPV infections,
45:46nearly an almost half of these
45:49are in people aged 15 to 24.
45:51These HPV infections will go on to
45:53account for **** genital diseases,
45:55including cervical, vulvar,
45:56and vaginal cancer, but also a high number.
45:59**** cancers as well that will
46:01affect both men and women,
46:02and I think that will should really
46:04be a theme throughout is really the
46:06impact that is also happening on men,
46:08especially for our audience who
46:10may have a practice where they
46:12see both men and women.
46:13But if their efficacy in
46:15this vaccine and how?
46:17What is the data show in terms of
46:20the prevention of these cancers?
46:21And we see that in people aged
46:2416 to 23 in multiple studies,
46:26those cancers that were HPV related.
46:28Specifically,
46:29there were significant efficacy in
46:31reducing the burden of HPV related
46:33malignancies as well in student awards,
46:35which are significant burden on
46:37both our patients but also in our
46:39health care system and millions of
46:41dollars expense annually on managing
46:43these diseases that are really
46:45preventable through primary prevention.
46:47So what are the indications according
46:50to the FDA and half of right now it
46:53is indicated for girls and women
46:559 through 45 and talk about the
46:58expansion to 45 for the prevention
47:00of the following diseases.
47:01So this is cervical, vulvar,
47:03vaginal, **** oropharyngeal,
47:04another head and neck,
47:06cancers related to HPV,
47:07as well as the benign but bothersome
47:10genital warts that are caused by the
47:136:11 subtype as well as prevention
47:15of the pre invasive disease of
47:17the lower channel.
47:19Tract is a very similar recommendation for
47:22boys. However, obviously know CI Nbin vein,
47:26but otherwise I'm very similar.
47:30Recommendation indication there?
47:31So where does the data come that helps
47:34us guide our decision making regarding
47:36the expansion of the vaccine towards
47:38people who are 24 to 45 and so in this
47:40study and this is a sort of end of study.
47:44Follow up paper looking at this age
47:46group specifically in women and they
47:48use the quadrivalent vaccine and we
47:50have no reason to believe that the
47:52efficacy will not be as good in the
47:55nano valent vaccine Gardasil Nine.
47:56They looked at a number of
47:58outcomes related to HPV.
48:00Section and here in the per protocol name.
48:02Besides that, because the intention
48:04to treat is a little bit different,
48:06we look at the observed efficacy of the
48:09vaccine in preventing a number of different.
48:12Outcomes and when we look at overall
48:15persistent infection or CNN or other
48:17disease of lower genital tract,
48:19the efficacy was about 88% a little better
48:22in those who are younger and a little less,
48:26and those who are older.
48:28However,
48:28the the impact CIN two or three or worse.
48:32Although listed as 83.
48:34Unfortunately those confident
48:35interval do cross one and so the the
48:39impact there may not be as strong.
48:41However you know.
48:42I've had many patients who come
48:44into my office.
48:45Not a lot of questions about this
48:47and they fit in that age category
48:48and we'll talk about how to address
48:50that on a very individualized
48:52individual risk assessment so that
48:54we can help women make informed
48:56decisions with the data that we have.
48:59So currently the CDC recommends
49:01that as of 2019,
49:03harmonization of catch up vaccination
49:06for appropriate persons through
49:08age 26 should be undertaken and the
49:11that group from 27 on 245 is really
49:14shared clinical decision making.
49:16So I saw a young woman recently
49:18in my practice who have been in
49:22a monogamist relationship since
49:24their first ****** encounter.
49:26She's now 2829 years old.
49:28Unfortunately,
49:29she.
49:30Gone through into 4th and it's
49:32reentering the dating and had
49:34questions about the efficacy of
49:36this and so we talked about that and
49:39through shared clinical decision
49:41making she decided to proceed
49:43with getting the vaccination.
49:44Now that's not to say that that
49:46is going to provide her the same
49:49efficacy of someone at the younger age
49:52category of the FDA recommendations,
49:54but she still falls within the CDC
49:57and the FDA recommendations and.
49:59I would encourage you to have those.
50:00Conversations with patients on
50:03a very individualized level.
50:05So there are a number of women
50:07nationwide still could benefit
50:09from updating their vaccination
50:10status through this catch up cohort
50:13and even more importantly,
50:14are a number of men and so for those
50:17of you who also take care of a
50:19man in your primary care practice,
50:22I would encourage you to consider
50:25this and when speaking with them about
50:28their overall primary prevention.
50:30We can't go through a talk in this
50:31time period without discussing
50:33safety of vaccine.
50:34It's on everybody's mind
50:35with the covid vaccine,
50:36but just to highlight that this is a
50:39very safe vaccine with very minimal
50:41side effects and low grade toxicities.
50:43So what can we do to increase vaccination
50:46rates here in Connecticut to try to prevent
50:48all of these HPV related infections?
50:51And more importantly,
50:52is HPV related building that sees and
50:54we want to assess the immunization
50:56status and for patients at each
50:58clinical encounter and then what I
51:00think is probably the most important
51:02is the recommendation of the provider
51:04and patients very much rely on
51:06your opinion in your and value your
51:08input into their decision making
51:10and so by educating yourself about
51:12this data in these recommendations.
51:14You'll be able to provide a strong
51:17recommendation is appropriate
51:18for that patient.
51:19We want to either administer within
51:21our own practices or refer onto a
51:23either a pharmacy or clinic that can
51:26provide vaccination and to ensure that
51:28our vaccination status is updated and
51:31documented for all of our patients.
51:33These measures are supported by
51:35ACOG and encouraged and there are
51:37a number of opportunities that you
51:39could look at in the evolution of
51:42their relationship with your patients.
51:44Beginning is when they transition
51:46from care from the pediatricians
51:48office into gynecological care,
51:50and so perhaps they did not or
51:52not offered or or did not accept
51:55vaccination in that earlier cohort
51:57than nine nine years and up.
52:00And so this transition into care
52:02interview I am practice is an
52:04opportunity to re address the data
52:06and and discuss that opportunity
52:08with patients when we're giving
52:11other vaccines brings up another
52:13opportunity to discuss.
52:14The increased use of HPV vaccination
52:16and we talked before a little bit
52:19about how Mcninja cockle vaccine
52:21given at a very similar age have
52:23very high rates of uptake.
52:25But we do not see that same experience
52:27with HPV and so by including HPV
52:29vaccination in the discussion at
52:31the same time will provide an
52:33opportunity hopefully to see increased
52:36rates of vaccination.
52:38As people are heading off to college,
52:40this provides another
52:42opportunity for counseling,
52:43either in combination with other counseling
52:45efforts regarding perhaps birth control,
52:47or pap smears,
52:48but this is another opportunity
52:50where you may be able to provide an
52:53opportunity for man or woman to become
52:56vaccinated prior to heading off to college.
53:00And like I said before,
53:01the greatest predictor in this
53:02affectionate and a lot of studies
53:04is really the recommendation
53:05of the health care provider,
53:07and so take that to heart and and
53:10patience really value that we're trying
53:12to make a decision on what to do.
53:15I'm definitely gonna laryngologist
53:16or any anti through my.
53:18I want to highlight how we're really
53:20trying to expand the messaging
53:21around vaccination to not just
53:23be related to cervical cancer,
53:25but the word in the HPV has on
53:28the number of other head and neck
53:30cancers into frame.
53:31Our discussions,
53:32more around HPV vaccination as a way
53:34to hopefully prevent a malignancy
53:36and less around the HPV infection
53:38itself and the stigma that may be associated
53:41with that for one reason or another.
53:43We see that there is a relationship between.
53:46HPV and cancers of the head and neck.
53:48And we see that the prevalence of different
53:51HPV types is very similar to what we
53:53see in our cervical cancer patients.
53:56Very interesting Lee.
53:57We've seen a decline of
53:59cervical cancer over the years,
54:00but are beginning to see an increased
54:03rate of oral, pharyngeal cancer,
54:05especially among men,
54:06and there are significantly more or
54:08fragile cancers diagnosed annually,
54:09which just brings even more
54:11importance to why we need to include
54:14that as part of our counseling.
54:16And when we're discussing the benefits
54:18that we can expect from HPV vaccination,
54:21males are affected 5 times more than females
54:24when it comes to these types of cancers.
54:27And so it really is behooves us to discuss
54:29these benefits at every clinical encounter.
54:32So if you're carrying for a mother who
54:34has a male child who is perhaps of the age
54:37that he could benefit from HPV vaccination,
54:41that's an important discussion that you
54:43can have as the primary care provider
54:45of the mother of the grandmother,
54:47whoever it is,
54:48and the more that we move this
54:50conversation towards HBF and infection.
54:52And HPV vaccination as a cancer
54:55prevention strategy.
54:55We hope to see increased rates
54:58of vaccination.
54:59And again, I think again, you know,
55:02I can't phrase it out any other
55:04way than just we have to try to,
55:06you know,
55:07provide our patients with all of the
55:09data in all of the information on the
55:11potential benefits of this cancer
55:13prevention strategy and hope that
55:14through that we can remove some of the
55:17stigma associated with HPV vaccination.
55:18And it highlights the importance
55:21for both men and for women.
55:23So with that in mind,
55:25and having you know,
55:26talked on and on about the importance of
55:28HPV and how it relates to cervical cancer,
55:31I do want to talk a little bit of both.
55:35The updated ASEP management
55:36guidelines and how they are really
55:38well summarized in what I think is
55:40a pretty easy to use app that you
55:43may consider incorporating into your
55:44practice and and as a way to help
55:46with stratify and provide patients
55:48with the most up-to-date information
55:50on the risk of cervical cancer.
55:52And so this app reflects the 2019.
55:55Updated guidelines and once in the
55:57greatest shift is it really highlights
55:59the incorporation in the important of
56:01test history into calculating risk.
56:04So you'll see and will provide an
56:06example tonight of how it looks,
56:09but it's not just about that one.
56:12Single smears a snapshot in time.
56:14The data is really supporting the use
56:16of understanding a woman's history of
56:19dysplasia in history of HPV infection.
56:21In order to really understand what is
56:25her individualized risk assessment.
56:27And so we've known for a number of years now.
56:31The HPV based testing strategies are
56:33certainly superior to cytology alone.
56:35This is really a Sentinel paper
56:37that highlighted that showing
56:39that on the bottom here we can
56:41see HPV and HPV Co testing in
56:44the incidence of Cinc predicted.
56:45The incidence of CI and three or more above
56:49in the pop history is well really matters.
56:52This is a paper currently impressing
56:54highlighted at the recent FGO meeting.
56:57Just highlighting the real importance
56:58in understanding the multiple
57:00prior screening events that a
57:02woman has undergone and trying to
57:04assess her individual life risk.
57:05And that's what this app really
57:07provides a chance to individualize.
57:09Some of the risk assessment so they
57:12can make appropriate decisions for
57:14themselves and so we see here on
57:16the left that a woman with three
57:19negative code tests really have a near
57:21negligible risk of a CIN 3 or above.
57:24Whereas someone who is HPV positive
57:26or persistently HPV positive or
57:28have had treatment for sin.
57:30Three or above lesion,
57:31certainly at higher risk than her well
57:35tested and Co test negative counterpart.
57:38And so this is reflected in the app
57:40and those who do have use dinner or
57:43review the guidelines can appreciate the
57:45differences in the recommendations and how
57:48things are looking compared to before,
57:50but it's really all about risk assessment
57:53as opposed to direct indications
57:55and recommendations on what to do
57:57next for treatment or or testing.
57:59So this is just a little example of how
58:02the app looks so on the left hand panel
58:05we've selected perhaps a woman who.
58:08Is 25 to 29.
58:09Although not a great example,
58:11'cause we should probably be focused
58:13on 30 to 65 if we're looking at
58:16the importance of HPV and then we
58:18select that and then we go down to
58:21indicate that we're interested in the
58:23management of routine screening results,
58:24and then we are able to select
58:26all of these different.
58:28All these different variables that
58:30will go into helping predict risk
58:32and what's new and important is the
58:34question of whether or not patient has
58:37previous screening results that could be.
58:39Input it into this algorithm to
58:41help us understand what to do next,
58:44and so our patient.
58:45Yes,
58:46she has been compliant with their
58:47screening and so we have entered
58:50her previous screening history.
58:52And so we go on now to include those
58:54prior test results in our recommendation.
58:57Based on what we've entered.
58:59If for one year follow-up,
59:01what's nice,
59:02and I think it's really helpful for patients
59:04in ourselves to understand the overall risk,
59:07is this second image.
59:09Which is the risk of CIN 3 or above,
59:13and with that we're able to
59:16appropriately treat her to next steps.
59:19So,
59:20just to summarize,
59:21I you know we've covered a lot,
59:23but I think really it's important to
59:26consider education and counseling
59:27on the benefits of vaccination.
59:30At each clinical encounter,
59:31as well as to stress the importance
59:33of a strong recommendation for those
59:36who are eligible really to emphasize
59:38the importance of this intervention
59:40as a cancer prevention strategy and
59:43to identify someone within your
59:45practice or your Community practice
59:46who can really champion this effort
59:49and then routinely reassess your strategies.
59:51And look for areas to improve
59:53effectiveness and I would encourage
59:54you to consider this app as one tool
59:56that you use in helping manage physical
59:59cancer screening your practice.
01:00:03So with that you know. Thank you so much.
01:00:06We're going to stop the share and
01:00:09open it up for questions either
01:00:11regarding our cervical cancer talk
01:00:13or anything that we've covered.
01:00:15Otherwise, this evening and and
01:00:17hope we can clarify any points
01:00:19or or answer any questions.
01:00:27I don't see anything in the chat right now,
01:00:31but will give it a couple more minutes again.
01:00:34If you have any questions I didn't put
01:00:37my email address out there, but please
01:00:40feel free to reach out to me directly.
01:00:43It's my name mitchell.clark@yale.edu
01:00:45and I'd be happy to help answer any
01:00:48questions or help you navigate referral
01:00:51process if if you're seeking tour
01:00:53for your patient to smile Center.
01:00:56For evaluation.
01:01:00And I don't see anything else unless
01:01:02China you have anything to add. Or yeah,
01:01:04doctor Clark. Thank you.
01:01:05I just wanted to give a shout
01:01:07out to a couple of our patients.
01:01:09I recognize some of our patients
01:01:11that are on tonight as well.
01:01:12And thank you for just being women who
01:01:14have been champions in our program and
01:01:17just getting the word out there that
01:01:19we can detect cancer earlier we can,
01:01:21you know, take really good care of you
01:01:23and we want you to be part of our family.
01:01:26So for the women who are out
01:01:27there that are patients,
01:01:29thank you for joining in.
01:01:31For people who don't know yet,
01:01:33we have something called discovery to cure,
01:01:35which is one of our programs that focuses
01:01:38on prevention and we do have a website.
01:01:41We have a something called the teal times,
01:01:44which is one of our newsletters that can
01:01:46go out to providers or or women and patients.
01:01:50So if you have any interest
01:01:52in getting connected with us,
01:01:54I'm happy to help connect you.
01:01:57Great yeah, I agree I I you know,
01:02:00really thank our patients for advocating
01:02:02for themselves and for others in
01:02:04the Community who aren't aware of
01:02:05the resources that are out there.
01:02:07And I think all of us are probably
01:02:09going to speak with John,
01:02:11but it's really our patients who
01:02:13motivate us and in their journey
01:02:15and their strength that is so
01:02:17motivating for us to do what we do.
01:02:19And it's such an honor to take care
01:02:22of these strong women who really
01:02:24are paving the way for future
01:02:26treatments or participation in.
01:02:28Trials and things like that.
01:02:30We have one question here from someone
01:02:33in the audience asking about any known
01:02:36connection between vulvar cancer
01:02:38in bracket two patients over 75.
01:02:41Typically,
01:02:42the older women with with bolvar
01:02:44cancer is typically related to the
01:02:47lichenoid diseases less related
01:02:49to HPV infections and join,
01:02:51and I don't think any strong
01:02:54Association known between predatory
01:02:56breast ovarian cancer genes.
01:02:58Are the HR jeans and involve our cancer?
01:03:02Now there's as far as we know,
01:03:04there's no Association with vulvar or
01:03:07vaginal cancers with genetics that only
01:03:09the only thing that may cause cervical
01:03:12cancer is one of the rare gene mutations.
01:03:14But when we think about hereditary
01:03:16breast and ovarian cancer syndrome,
01:03:18or Lynch syndrome were thinking ovarian,
01:03:20fallopian tube, and uterine cancers.
01:03:25That's great, great question.
01:03:26Thank you for bringing it to our
01:03:29attention where you know we're learning
01:03:31more and more about these and we look
01:03:35forward to seeing expanded results from
01:03:37years of experience in genetic testing.
01:03:40And so this may involve overtime for sure.
01:03:44Another great question from one of
01:03:46our best practice nurses regarding
01:03:48HPV vaccine and age.
01:03:49Any studies showing benefit to vaccine
01:03:52earlier at age 9 rather than 11?
01:03:54You know I don't have the the sort
01:03:57of original paper up in front of me,
01:04:00whether or not they broke those groups
01:04:03down like they did in the trial here,
01:04:05showing benefit to 26 to 35 at
01:04:08the post of 35 to 45.
01:04:10I think really the overall
01:04:12thinking is to try to get this.
01:04:14In its earliest possible,
01:04:17before any exposure to HPV.
01:04:20And as soon as we can do that,
01:04:23the better so that we do know that those
01:04:26people who are enrolled in the trials
01:04:29of HPV vaccination those who were.
01:04:31HPV naive certainly had a better
01:04:33response at clearing that infection.
01:04:35And so while I don't have any data to
01:04:38think 9 birth 11 off the top of my head,
01:04:41I think as early as possible within
01:04:44the recommendations of the FDA and CDC.
01:04:49We have another great question from
01:04:52someone asking about the role of
01:04:55heated chemotherapy during surgery.
01:04:57That's a great question and evolving topic.
01:05:01This was one of the first RCT's that we
01:05:04presented here tonight from one of the
01:05:08European groups and we are excited to
01:05:11offer this on selected patients through
01:05:14Smilow who are meet good criteria
01:05:18will have good performance status.
01:05:20And who meet certain eligibility
01:05:22eligibility criteria?
01:05:23Sorry bout that everyone and that
01:05:26is certainly something that should
01:05:28be brought up with your treating
01:05:30uin oncologist in order to determine
01:05:32if you might be a good candidate
01:05:35for that type of approach,
01:05:37because there is early data that
01:05:39signals there may be benefit for
01:05:41those patients who who are deemed
01:05:44eligible for that for that technique.
01:05:49We have another great question
01:05:50from someone talking about the
01:05:52difficulty with carbon emitters.
01:05:54Any recommendations on
01:05:55improving patient tolerance?
01:05:56That's a great question.
01:05:57So in terms of carbon hitters,
01:06:00what I tell most of my patients is those
01:06:02first four to six weeks can be very
01:06:05challenging and it's really the fatigue.
01:06:08I find the most part that patients
01:06:10struggle with a bit of the nausea
01:06:13as well because of the fact
01:06:15that this is an oral medication.
01:06:17Most patients do.
01:06:18Seem to get through the first four
01:06:21to six weeks with either, you know,
01:06:23watching the anemia to ensure
01:06:25that that fatigue is not true.
01:06:27I mean,
01:06:27for watching the moment to make sure
01:06:30that the fatigue is not anemia related,
01:06:32but for those who don't make it through
01:06:34that sort of introductory first couple
01:06:36of months and still continue to struggle,
01:06:39there has been some exploration of perhaps
01:06:41switching from one partner to another.
01:06:43We think overall the side effects
01:06:45are somewhat of a class effect,
01:06:47but there are some very small.
01:06:49Series and experiences,
01:06:50and perhaps going a lap criptana wrapper it,
01:06:53or vice versa if you can get that approved
01:06:55based on whatever genetic profile
01:06:57you're dealing with in that patient.
01:07:00But you know for some reason or another,
01:07:02some patients just seem to tolerate one
01:07:04better than the other, and so you know.
01:07:07I tell my patients to hold,
01:07:09hold out if they can,
01:07:11and we try to support them through
01:07:13the first four to six weeks.
01:07:15But if there's persistent grade
01:07:17three Grade 4 toxicity,
01:07:18you could consider.
01:07:19Perhaps switching to a different
01:07:21a different formulation,
01:07:23but again that would be depending on
01:07:25approval and and and what molecular
01:07:28characteristics here you're working with.
01:07:36The great questions from everyone.
01:07:38I really appreciate the discussion.
01:07:43I think we're pretty much it for now,
01:07:46so again, please feel free to reach
01:07:48out if you have any questions regarding
01:07:50the material we covered tonight or
01:07:53you have a question in general,
01:07:54will try to get that answer for you and we
01:07:57really appreciate you joining us tonight.
01:08:00We're really excited about
01:08:01how things have evolved.
01:08:02I could have never imagined even you know
01:08:05when I decide to be human oncologist
01:08:07that we will be talking about these
01:08:09advances so quickly and we really
01:08:11hope that we evolve things at a pace.
01:08:15That keeps women alive longer
01:08:16and joining back quality of life.
01:08:18And until we can treat this like a
01:08:21chronic disease like anything else.
01:08:24Alright, so thank you so much for
01:08:26everyone and we hope to see you soon.