Imaging, Radiation, and Reconstruction

June 21, 2021

Information

June 18, 2021 | Drs. Regina Hooley and Christin Knowlton

ID6738

To CiteDCA Citation Guide

00:00Soon my name is Mara,
00:02Gulshan here at Yale University,
00:05Yale Cancer Center,
00:06Smilow Cancer Hospital.
00:07Welcome you to the third
00:10breast CME lecture series.
00:13This today we're really fortunate to have
00:16three phenomenal speakers and panelists.
00:18We're going to start with
00:20Doctor Regina Hooley,
00:21who's professor of Radiology vice chair
00:24in the Department of Radiology in the
00:27interim as division Chief for breast imaging,
00:29and then we go to Doctor Kristen Knowlton,
00:33our medical director for Radiation
00:35Oncology at Yale at Hamden,
00:37and then last but certainly not least,
00:40Doctor Tomer Abraham,
00:41who is our director of breasts.
00:44Microsurgical reconstruction and
00:45breast reconstruction here at Yale.
00:47The format is that will have
00:49three consecutive speakers.
00:50I really encourage you to put as
00:53many questions as you want into the
00:55chat box or the question to answer.
00:58Box will try to answer them as
01:00much as possible in real time.
01:02Some will leave two to the
01:04end for discussion,
01:06and with that I really appreciate everyone
01:08taking the time to to log in and listen.
01:11This is going to be recorded
01:14so you can go back.
01:16If you want or share this with
01:18friends and colleagues around the
01:20country and around the world,
01:22so with no further ado,
01:24we'll turn it over to doctor Doctor Hooley.
01:29OK, thanks so much doctor Golshan.
01:32It's really great to be here,
01:35so I'm going to start by sharing my
01:38slides and let me just get this.
01:41Uhm? Why OK? So?
01:44I'm going to talk a little bit about
01:47breast cancer screening and, you know,
01:49one size no longer fits all these days.
01:52There's we're moving towards a
01:54more personalized screening,
01:55so I'm going to review screening
01:57it and show you where it's going
02:00over the next 20 minutes or so.
02:03My disclosures I am on the Medical
02:06Advisory Board for dense breast dot
02:08dash info and that's where I took
02:10some of my tables and figures from.
02:13That's a website that has a lot
02:15of information on screening.
02:17It's accurate and it's for
02:19patients as well as providers.
02:22So I'll start by reviewing the
02:24background breast cancer course.
02:26Worldwide is the most common cancer in women.
02:29It accounts for about 1/4
02:31of all female cancers.
02:33Is the leading cause of cancer
02:35related mortality worldwide?
02:36About 15% of all female
02:38cancer deaths in the US.
02:41Lung cancer is number one
02:43for cancer related mortality,
02:44and interestingly,
02:45the rates of breast cancer is rising
02:48worldwide at about 6.4% per year.
02:51Nobody really knows why,
02:53but that adds up.
02:56The World Health Organization reports
02:57that in 2018 there were 2,000,000 cases
03:00of breast cancer diagnosed worldwide,
03:03and by 2040 that'll rise to 3,000,000,
03:06so it is significant.
03:08In general,
03:09the incidence of breast cancer is
03:11more frequent in developed countries,
03:13as noted on the blue map on the left,
03:16and this is likely due to
03:18screening mammography.
03:19However,
03:19women diagnosed in developing countries,
03:21as noted on the map on
03:23the red map on the right,
03:26are more likely to be diagnosed
03:28at an advanced age and are more
03:30likely to die from the disease.
03:32And maybe this is because there
03:34is pretends not to be formalized.
03:37Breast cancer screening in
03:39these developing countries.
03:41When it comes to breast cancer
03:42screening and mammography,
03:43we've certainly come a long way.
03:46Breast cancers.
03:48Screening and mammography was first
03:51introduced, probably in the 1960s,
03:53and this is a paper from 1967
03:56showing the new technology.
03:58At the time there was film screen,
04:01mammography, and zero mammography as well.
04:04Pretty basic stuff that,
04:05compared to our standards today.
04:08But even those studies were
04:10able to show some cancers.
04:13Of these days,
04:14of course,
04:15Thomas synthesis or the 3D mammogram
04:18digital breast tomosynthesis is
04:20becoming the standard of care
04:22where we can see explicit detail
04:25of the breast tissue as well as.
04:27Small or or subtle cancers that
04:30are not well seen on the 2D
04:33traditional mammogram alone.
04:34Our group at Yale was lucky to be
04:37one of the first centers in the
04:41United States to get tomosynthesis.
04:43I think it was back in 2011 and
04:46a few years after that we became
04:49fully all of our mammograms were
04:52tomosynthesis and we were leaders in
04:55publishing led by Doctor Leon Philpotts.
04:58And so showing that tomosynthesis
05:00is beneficial
05:01for screening and diagnosis of breast
05:04cancer among all women and among all ages.
05:10Some screening mammography
05:12has been shown to save lives,
05:14multiple randomized control trials,
05:15and observation.
05:16ULL studies have shown that breast cancer
05:19mortality is increased by about 20 to 40%.
05:21Is the only test that has been shown a
05:24clear mortality reduction of breast cancer,
05:26and this is mostly due to downshifting
05:29up stage two and hired a stage one.
05:32There are fewer node negative.
05:34There are fewer negative invasive cancers,
05:36less tumor process, better tumor biology.
05:38And among screening detected cancers
05:4075% or stage zero DCIS or stage one
05:43and among clinically detected cancer is
05:45more than 50% are stage two or higher.
05:49And here are some examples
05:51of some mammograms in women.
05:52On the left hand side of the screen.
05:55This is a 67 year old woman who had
05:57never had a screening mammogram.
05:59She is a palpable 4 centimeter mass.
06:02It's pirates 5. We know it's a cancer.
06:04This was a triple negative,
06:06high grade cancer and we would think
06:08that she would have, you know,
06:10regular speeding. Agra fee.
06:11We would have caught this at an earlier
06:13earlier stage and smaller size.
06:15On the other hand,
06:16in this patient there's a tiny new
06:18group of calcifications there.
06:20Linear their branching.
06:21She's 15-6 years old.
06:22She has a screening mammogram every year,
06:25so they're caught earlier,
06:26and this was a very tiny 1.5 millimeter
06:29grade, two cancer, High Ki 67.
06:31So presumably this is a life
06:34saving mammogram in this woman.
06:36So despite the success of mammography,
06:38it is imperfect,
06:39is particularly limited in
06:40women with dense breasts.
06:42The overall false negative rate
06:44of mammography among all breast
06:45densities is about 10 to 15% in
06:47the overall sensitivity is 70 to
06:4990% dense breasts make it hard for
06:51us because of the masking effect
06:53where cancers tend to be white spot.
06:56So there can be difficult to see
06:58with the white fiber glandular
06:59tissue versus women with non dense
07:02breasts where there's more fat and
07:04less white gland or tissue.
07:06And cancers are easier to identify.
07:09So screening mammography is very
07:11controversial, controversial.
07:11I think we all know that our
07:15patients know that it's hard to
07:17miss the articles in the.
07:19And in the press.
07:21Over the past decade or so,
07:24and screening has become more complicated,
07:27and this step partially because of the
07:30United States Protective Services Task Force,
07:33who first issued recommendations
07:35on screening mammography in 2009
07:37and then reinstated them again,
07:39didn't change them.
07:40Basically,
07:41in 2015 and basically gave screening
07:43mammography, AB, and even a C rating.
07:47They basically said that having
07:49a annual screening mammogram and
07:52women in there.
07:5340S was a C grade,
07:55meaning that this service might be.
08:00Offered in selected patients.
08:02Depending on some circumstances
08:04and then gave screening mammography
08:06every two years from age 50 to 74
08:10AB grade and you know when we're in medicine,
08:13we generally like A's that we should
08:16be offering this.
08:17But you know Decencies and also the
08:21changing recommendations didn't
08:22really sit right over all the task
08:25force again.
08:25Recommended against screening
08:27mammogram of women in their 40s.
08:29They also recommended against teaching
08:32self breast examination they were against.
08:35Clinical breast examination.
08:36There were against screening women over
08:39the age of 75 and they were really
08:43only for screening women every other
08:45year in the starting age 50 to 74.
08:48This is very controversial.
08:50Patient advocacy groups primary care,
08:52oncology, radiology. Perhaps?
08:53It was really just about saving money,
08:56because it's certainly the less we screen,
08:59the more money we're going to
09:02save on healthcare dollars.
09:03And in all fairness.
09:05These recommendations are very similar to
09:07other countries that have nationalized
09:08health services and health programs,
09:10but we don't have that
09:12here in the United States.
09:13So saying that this is what we
09:15should do in in a country that
09:18doesn't have a full National Health
09:20Service doesn't seem to be fair,
09:22and not mentioning that at
09:24all doesn't seem fair.
09:26I do want to focus on the fact that we really
09:29should be screening women in their 40s,
09:31and if there's one thing that you
09:33should take away for anyone who doesn't
09:36believe in screening women in their 40s,
09:38we need to screen women in
09:40their 40s every year.
09:41So, so please take, you know,
09:43lock this in from this,
09:44talk women in their 40s have
09:46higher interval cancer rates.
09:48They have denser breasts.
09:49We know that interval cancers that are
09:51diagnosed between having a normal mammogram.
09:53These are usually symptomatic.
09:54Cancers tend to be more aggressive.
09:57Cancers in women have a shorter sojourn time,
09:59and they tend to be faster growing.
10:02We also know that.
10:05There's higher survival for earlier
10:07stage tumors, and, importantly,
10:08there's ethnic differences.
10:10Black and Hispanic women have a peak
10:13incidence of breast cancer in ages 46 to 47,
10:16so telling having a sweeping
10:18statement that says,
10:19you know we should only start
10:22screening at age 50 is really doing
10:25these patients a major disservice.
10:28Uhm?
10:30Here this graph shows that you
10:32know breast cancer in the 40s,
10:35accounts for about 20% of
10:37all invasive breast cancer,
10:38so it is a considerable fraction
10:41of the disease burden.
10:42So it is very important.
10:45So the screening guidelines,
10:47as they stand now.
10:49Among various organizations,
10:50looks kind of confusing in this table,
10:53but it's pretty.
10:56Think it's really pretty straightforward.
10:58Basically, most organizations
10:59say you should start at age 40,
11:02and with the exception of the
11:04task force were offer it.
11:06So again,
11:07this this reflects the patient
11:09shared decision making with ACOG
11:11and the American Cancer Society
11:13has the option also discharge date
11:15page 40 and says really start
11:18annual screening at age 45,
11:19so the American Cancer Society sort of
11:22bridge the gap between societies like
11:25the American College of Radiology.
11:27And the United States Protective
11:29Services Task force.
11:30Life expectancy is a little bit
11:32all over the place.
11:33I'm not so sure something
11:35magical happens at age 75.
11:36I think it's better to limit
11:39screening when life expectancy
11:40is less than 10 years,
11:42because we know these patients
11:43are not going to really benefit
11:45as much from early detection.
11:47So we have healthy patients who
11:49might be 76 years old and they
11:51should still have a mammogram,
11:53perhaps, maybe not annually.
11:55Perhaps we can even consider
11:57every one to two years.
11:59And then we have patients who might
12:01be 70 or 69 years old or whatever,
12:03or not that healthy.
12:04And maybe don't need to
12:06have a mammogram as well.
12:08And again, as far as the interval goes,
12:11most people say annually,
12:12maybe every one to two years the
12:16the task force being the extreme
12:18of every every other year.
12:20So in addition to the variable
12:23mammographic screening recommendations,
12:24supplemental screening is also an
12:26option for many of our patients.
12:28This includes ultrasounds and MRI.
12:30There's also newer technologies
12:32such as molecular breast imaging
12:33and contrast enhanced memo that are
12:36really investigational at this time,
12:38but they are on the verge of being
12:41offered outside of the screening trials.
12:43There are limited screening
12:45trials that are going on.
12:47So these tools are right around the corner.
12:50I believe for more widespread use,
12:52widespread clinical use,
12:53but I'm only going to review
12:56screening ultrasound and MRI today
12:58because of the time constraints.
13:00So breast ultrasound screening is linked
13:02to death dense breast notification laws.
13:04We do a lot of breast ultrasound
13:06screening in Connecticut because
13:07we were the first state to have
13:09a breast density notification
13:10law which was passed in 2009.
13:12Coincidentally the same month
13:14that the United States Protective
13:16Services Task Force told us that
13:17we should stop screening women in
13:19their 40s and then we have the
13:21Connecticut State saying that we
13:23should be offering patients with
13:25dense breast screening ultrasound.
13:27The restless notification.
13:28Just as an aside,
13:30has become quite popular,
13:31I think over 30 states in the United
13:34States have breast density notification laws.
13:37There are countries in Europe and South
13:39America that are considering breast.
13:44Density notification guidelines as well.
13:48And women with dense breasts do benefit
13:51from having a screening ultrasound.
13:53Overall, the cancer detection rate is about
13:55two to four per thousand women screen.
13:58This is in addition to the approximate
14:005 cancers per thousand women
14:02screen detected on mammography.
14:04We know that most cancers detected on
14:07screening ultrasound are small and node
14:09negative and tend to be early stage,
14:11so it's rational to think that
14:14finding these mammographic Leopold
14:16cancers at an early stage in smaller
14:18size will improve overall mortality.
14:21Ultrasound screening is really
14:22well accepted by our patients.
14:24It's relatively inexpensive.
14:25It costs about the same price as a mammogram.
14:28There's no Ivy contrast.
14:30There's no compression.
14:31It's widely available, so it can work.
14:35Which is why we offer it to our patients.
14:39It also performs very well in
14:41women with dense breast tissue
14:43before the mammogram is limited,
14:45and that's because of the
14:47contrast on ultrasound.
14:48These small cancers on ultrasound
14:49tend to be dark or hypoechoic,
14:52and dense breast tissue tends to look
14:54echogenic or white on the ultrasound,
14:57so we can see these little cancers that
14:59are draped in the glandular tissue fairly
15:02well and they will be mammographic.
15:04Leah called because they're just hiding
15:08behind this glandular tissue as well.
15:11Breast density is also important,
15:12so I just want to review this briefly
15:15because most of our more personalized
15:17community in the direction that we're
15:20going to go to is going to include
15:22breast density as a factor in what
15:24kind of screening patients should get
15:26breast dense breasts is very common.
15:29It's seen in about 50% of all
15:31women in the United States.
15:33We know there's an increased
15:34risk of breast cancer in women.
15:37It's a 2/6 times increased risk,
15:39and it can be confusing.
15:41When you see what they did,
15:43you know two times increased risk and
15:45then we'll see another article that
15:47says four to six times increase risk,
15:49and that's because it really depends
15:51on what breast density category
15:53you're comparing.
15:54So if you compare women with extremely
15:56dense breasts with women with fatty tissue.
15:59Then the increased risk of developing
16:01breast cancer for women with extremely
16:03dense breasts is 4 to 6 times higher
16:06than the women with fatty breasts.
16:08However,
16:09that's the minority of our patients
16:11in the United States.
16:12Only about 10% of women have extremely
16:15dense breast tissue and only about
16:1710% of women have fatty tissue.
16:19So 80% of our patients have
16:21heterogeneously dense breasts or
16:23scattered fibroglandular tissue.
16:25And so if you compare women with
16:27heterogeneously dense breasts with fatty
16:29with with scattered fibroglandular,
16:31then you have only about two
16:33times increase risk.
16:34So that's why that risk is variable,
16:36so it does.
16:37It is considered however,
16:39a intermediate risk factor for breast cancer.
16:41It limits the mammogram.
16:43There are higher interval cancer
16:44rates and worse prognosis for
16:46these clinically detected cancers.
16:48So that's why breast density
16:49is important and it can only
16:51be diagnosed on a mammogram.
16:53It can be diagnosed based on.
16:56A breast exam and if the patient's breast
16:58exam is sort of lumpy and difficult to do.
17:01Another option for women with dense
17:03breasts is fast MRI screening.
17:05It has been proposed for average risk.
17:07Women with dense breasts.
17:09It is been being done clinically
17:11in other parts of the country.
17:13There's very little of it done
17:15in Connecticut, but for example,
17:17University of Pennsylvania does a
17:19lot of fast, summarized meeting
17:20for women with dense breasts.
17:22The first study was published
17:24back in 2014 by Christiana Cool.
17:26She's a highly regarded a radiologist
17:28in Germany an she showed that with a.
17:31Very fast acquisition time of three minutes,
17:33as opposed to about the the acquisition
17:36time or scanning time of a traditional MRI,
17:38which is about 10 or 15 minutes.
17:42We could detect cancers at a very
17:45high rate of 18 per thousand,
17:47and this has been replicated
17:49by other studies as well.
17:51So overall, the cancer detection rate
17:53of MRI's about 15 to 18 per thousand,
17:56which is higher than screening ultrasound.
17:58That supplemental yield is only
18:00about two to four per thousand.
18:02But MRI is more expensive and
18:05requires Ivy contrast.
18:06There's not a lot of MRI scanners
18:08out there as opposed to ultrasound,
18:11so it's not as.
18:12Easy to perform.
18:13Patients may not like it as well.
18:16Takes longer,
18:16but it does work.
18:18The two year validation showed there
18:20were no interval cancers so it was
18:22really catching all those cancers.
18:24The sense the negative predicted
18:26value was high and the specificity
18:28and positive positive predictive
18:30value are also very good as well.
18:32So here is a 61 year old patient
18:34with a pathogenic BRACA mutation
18:36and Paris producting something over
18:38ectomy with a negative mammogram,
18:41and she had a MRI six months later
18:43and they saw this little cancer and
18:46detected this so it can work in women
18:49with dense breasts and this woman.
18:52She also had high risk and which is
18:54where we do most of our breast MRI in
18:57our practices for high risk screening,
19:00and that's traditional.
19:02I was screening MRI for high risk patients.
19:05Here's the list there Braca positive
19:08patients they they have some of these
19:10syndromes may have chest radiation,
19:12usually eight years earlier,
19:14part age 30,
19:15an overall lifetime risk of
19:17greater than 20% high risk women.
19:19We recommend that they have an annual
19:22mammogram and MRI beginning around age
19:2425 to 30 and again this is the BRACA
19:27positive patients and another high
19:29risk patients and this is recommended
19:32by the American College of Radiology
19:34and the American Cancer Society.
19:36We also know that it's reasonable
19:38to delay the onset of mammographic
19:40screening until the age of 30.
19:42In some of these patients,
19:44and that's because of the radiation risk.
19:46These patients are known to have
19:48increased radiation sensitivity,
19:49particularly the BRACA one carriers
19:50and the P53 carriers, as well.
19:55So breast cancer risk
19:56evaluation is a growing program.
19:59Most more and more breast centers today are
20:02offering breast cancer risk assessment.
20:05This is in lieu in in coordination
20:07with interest in population health.
20:10We're doing more screening not
20:12only for breast cancer, but colon,
20:15cancer, and other cancers as well.
20:18So with breast cancer risk evaluation,
20:21there are multiple risk assessment
20:24tools that are very available online
20:26and the estimated risk can really
20:29vary depending on which model you use.
20:32Most centers are going for the tire
20:35acoustic model that's most widely
20:37used and that also incorporates
20:39breast density into that model.
20:42When we think about breast cancer risk,
20:45we have to know that risk changes overtime.
20:49Unknown risk and change every year.
20:51For example,
20:51you can have a patient who is just an
20:55average risk and then her sister was
20:57diagnosed with breast cancer at age 39,
21:00and that's going to bump up her her
21:02risk for breast cancer the following
21:04year and overtime the lifetime risk
21:07increases decreases, excuse me,
21:09but the five and 10 year breast cancer
21:12risk is also proportional to age,
21:14so it's complicated and that's
21:16something that I think most breast.
21:19Centers,
21:19including our own will be doing
21:21within the next 5 to 10 years,
21:23so we're really moving beyond just starting
21:26at age 40 and having a mammogram every year,
21:29which is nice and simple,
21:30and it's nice for you know,
21:32buzzwords and things like that,
21:34and advertising to something like this,
21:36which looks really complicated,
21:37but it's really not that complicated,
21:39so let me just review with you.
21:42Review this with you.
21:43So the first question is,
21:45does the patient have at least
21:47a 10 year life expectancy?
21:49If not,
21:50then she would only have breast imaging is
21:52there's a clinically suspicious finding.
21:54The majority of our patients will have a
21:5610 year life expectancy and then we ask,
21:59is she under the age of 25?
22:01A 75?
22:01If not,
22:02she's over age 75 with healthy then
22:04maybe she would have an annual
22:06or BI annual mammogram.
22:07Most of our patients are going to
22:10be under the age of 75 and then
22:12we're going to look at the wrist and
22:14if she is at high risk for breast
22:17cancer then we would recommend
22:18annual contrast enhanced.
22:19MRI beginning at age 25 or 30 and
22:22mammography beginning at age 30,
22:24she can't have an MRI because it's she
22:26can tolerate it or for whatever reason.
22:29Then she would have an annual screening
22:31ultrasound in addition to her mammogram.
22:33The majority of our patients that
22:35we are not going to be increased
22:38risk and so then we want to be sure.
22:41That they are under the age of
22:43over the age of 40.
22:45If they're not over the age of four.
22:47If they're not over the age of 40,
22:50and we would just tell them to
22:52start really screening at 40 at 40,
22:54we do the baseline mammogram.
22:56Of course,
22:56we always want to synthesis if
22:58it's available,
22:59and if she has dense breast tissue,
23:01then we would also offer them
23:03screening ultrasound or at some
23:05places screening MRI as well.
23:06So that's the algorithm
23:08where it stands today.
23:10What about the future?
23:12There are going to be more screening options.
23:15We're going to have advancing knowledge
23:17of genetics so it will be better risk
23:19assessment and more personalized
23:20medicine will have new technology.
23:22As I mentioned, molecular breast imaging,
23:24contrast enhanced mammography,
23:25and of course AI will be more patient,
23:27shared decision making.
23:28We're going to be talking more patience
23:30and helping them filter information,
23:32medical information and guide
23:33their decisions.
23:34And of course, health.
23:36Health care economics is going to play a
23:39part in how we screen our patients as well.
23:42And what makes the most sense?
23:46Briefly, I'm just going to
23:47touch on overdiagnosis.
23:48I know that there's some people probably
23:50listening and thinking we shouldn't
23:52screen so much because of overdiagnosis.
23:54We could talk entire day about overdiagnosis,
23:56but I've condensed it into two slides,
23:58and here's an example of a case
24:01of over diagnosis of 59 year old.
24:03She had a mass president or left
24:05outer breast stable for five years.
24:07It looks just like a little lymph node.
24:09We do tomosynthesis the first
24:11time she has atomo exam,
24:12and there's little speculations.
24:14And this turns out to be a great two tubular.
24:17My cancer probably would have done anything.
24:20It's a low grade cancer and so perhaps
24:22this is a true case of overdiagnosis.
24:26We know that some screening detected cancers
24:28may never become clinically evident.
24:30They Sgro very slowly with patients
24:33that die of something else before
24:35cancer becomes symptomatic.
24:37This example would be low grade
24:39DCIS in an elderly patient.
24:41We might over treat these patients and give
24:44him and subject them to potential hard.
24:47But the key is we don't know yet
24:49which low grade cancers will become
24:51lethal and when they'll become lethal,
24:53and so hopefully more research
24:55will be able to.
24:57To identify these cancers so that we'll know
24:59more where we need to really treat them.
25:01Where we can stand back a little bit.
25:05AI tools and population health and
25:07new technology are going to allow
25:09us to screen smarter.
25:11We're going to know who needs
25:13more and who needs less screening,
25:15but it's going to take a lot of outcome
25:18analysis and sufficient data right now.
25:21Our data collection is not that great.
25:23Most of the cancer registries that.
25:28Collect information on cancer.
25:29Breast cancer. Do not look at the
25:31method of detection so we don't know
25:33how these cancers are being diagnosed,
25:36whether they are palpable
25:37or whether they had to mow,
25:39or that whether they were diagnosis
25:41on screening ultrasound or MRI.
25:42So the American College of Radiology is
25:45working to include method of detection
25:47in the BI RADS and then when we do that,
25:50hopefully the cancer registries
25:51and the national databases will
25:53accept this so that we can collect
25:56information on new technology and
25:58figure out what works and what doesn't.
26:00So in summary,
26:01annual screening mammogram beginning
26:02at age 40 saves the most lives
26:04women with dense breasts have
26:06the option to choose supplemental
26:08screening ultrasound or MRI,
26:09high risk women benefit from annual MRI
26:11in addition to screening mammography.
26:13Often this will start before
26:15the age of 40 and just one key.
26:17If a patient is having a supplement,
26:20an MRI in addition to our mammogram,
26:22she really doesn't need a
26:24screening ultrasound as well.
26:25We know in the future,
26:27vascular based imaging
26:28will become more common.
26:30It's interesting vascular based
26:31imaging may not necessarily require
26:33Ivy contrast routine breast cancer
26:35risk assessment will probably be
26:37available to all women and artificial
26:40intelligence will definitely enhance
26:41the delivery of breast cancer
26:43screening at multiple levels.
26:45From effective efficient scheduling
26:47to managing and analyzing new data to
26:50helping the radiologist read better
26:51and faster and more accurately,
26:53and also again help us determine
26:56who needs what when so that we can
26:59really serve our patients very well.
27:02So I want to thank you for your
27:04time and attention and will be
27:06available for questions later.
27:08Thanks, thank you Doctor Holy,
27:10that
27:10was fantastic. I mean honestly,
27:12the the amount of work that the
27:14our breast imaging colleagues
27:15and yuan in our group and others
27:18have done is is truly remarkable.
27:20And there's just so much new excitement
27:23in the pipeline and kind of figuring out
27:26what the next steps are going to be great.
27:29Next, move on to Doctor Knowlton to
27:32discuss some of the recent changes and
27:36advances in radiation therapy and.
27:39The floor is all yours.
27:46Hope you're on mute still.
28:18So while we're waiting
28:20for the slides to pop up.
28:24Regina, what are your thoughts
28:25on how to screen an elderly
28:27woman after an index cancer?
28:29For example, an 85 year old with a newly
28:32diagnosed breast cancer after treatment,
28:34does she need follow up image in?
28:37This is from Doctor Berger. Really
28:39great question.
28:40Yeah so generally women you know around
28:4285 or 86 their their life expectancy.
28:44Even healthy women is probably around
28:46six or seven years where the benefit of
28:49early detection probably is not useful.
28:52That said, I think it really depends on.
28:54On how healthy the patient is,
28:56maybe she still likes having a mammogram
28:59love these older ladies of her healthy.
29:01They still want to come in and get
29:03their mammogram maybe every other year.
29:06I just wouldn't push it,
29:07but there is still some shared decision
29:09making there got it excellent.
29:14Hopefully you see my slides properly now.
29:17Looks great. OK, great, thank you.
29:19So my title is as you can see is
29:22deescalation of radiation therapy
29:24for breast cancer for breast cancer.
29:27At less is more.
29:32OK so I have no conflict of interest to
29:35report related to this presentation an any.
29:38I do not unfortunately have as many awesome
29:40pictures as our two other presenters.
29:43However, any pictures that were used
29:45here were taken from sites that allow
29:48use of their photos in this setting.
29:51So when I after the title was submitted,
29:54you know D escalation in the setting of,
29:57you know, radiation therapy in
29:59the setting of breast cancer.
30:01I actually looked up the word
30:03deescalation and I think maybe my title
30:05is not grammatically correct because
30:08Merriam Webster Dictionary does not
30:09say that this is a noun in anyway
30:12and I tried hard copy and online.
30:14It is a will say that it is a verb that
30:18can mean to limit to decrease in extent.
30:22Are to decrease in volume or scope.
30:24I was able to find a definition for
30:26the noun in the free dictionary,
30:29which is a reduction in intensity.
30:31So if we have any people that are
30:33very much on top of their grammar
30:35and my title may not be correct,
30:38I will say however that the title is more
30:41in the spirit of the Marian Webster.
30:44Definition where we are in the modern era,
30:48aiming to limit the radiation limit,
30:51the number of fractions limit the
30:53dose that they treatment volumes and
30:56also omit radiation when necessary.
30:59Really the free dictionary definition
31:01doesn't make sense because we're
31:04not really reducing the intensity
31:06of the radiation.
31:07What we do when we are changing the
31:11fractionation to a shorter fractionation
31:13is we are using newer schemes of radiation.
31:17To deliver the same biological
31:19effective dose so I do not feel that
31:22the free dictionary definition really
31:24beats what's happening in radiation.
31:26But the Marian Webster one does.
31:29So here we see, this is how we are D.
31:33Escalating as I had mentioned with
31:34the decrease in number of fractions
31:36decrease in volume of tissue treated
31:38an omission of radiation therapy
31:41for appropriate candidates.
31:42And this really does fit the less
31:44is more if we have less radiation
31:47we will have increased compliance.
31:49People will have if the fractionation
31:51scheme is more convenient for them,
31:53whether they have traveled issues
31:55or working issues.
31:56We're going to have more patients
31:58that will be able to get it with less.
32:01Stress there will be increased
32:03acceptance of the treatment course
32:05increased time for patients to work
32:08or to pursue their hobbies or take
32:10care of their families and increase
32:13quality of life.
32:16So moderate fractionation
32:17is now really old news.
32:19At this point, we've all seen it.
32:22This is what it is now.
32:24Truly in the United States,
32:26the new standard of radiation therapy
32:28for the intact breast standard or
32:30conventional radiation to the whole breast.
32:33It was for several decades,
32:3550 Gray and 25 fractions,
32:37meaning that the patient
32:38needed to come for five weeks.
32:41And then there would be an optional
32:44tumor bed boost of an additional
32:4610 to 16 Gray and five to 8.
32:49Actions which many women have
32:51received over the years,
32:52so that's six to six and a
32:55half weeks of daily treatment.
32:57Moderate fractionation for whole
32:59breast irradiation therapy,
33:00which I'd like to stress in at this
33:03time is without including the nodes.
33:06This is the new standard where we
33:08where the whole breast is being
33:11treated in 40 grey and 15 fractions
33:14or 42.5 Gray and 16 fractions.
33:16That's really institutional preference.
33:18Our institution at Yale we use
33:21the 40 grey in the 15 fractions
33:24from the start B trial,
33:25and for these patients there's
33:27an optional tumor bed boost 10
33:30Gray and for fractions.
33:31So we're taking the standard or
33:34conventional fractionation of five
33:36to six to six and a half weeks,
33:38and now it's become three to
33:40four weeks for the patient.
33:44And of course there's some
33:46data to back all of this up.
33:49These are the three largest trials
33:51that have the longest follow-up that
33:53are used to backup or support the
33:56use of moderate hypofractionation.
33:58All three trials to start a the start B, and.
34:02There's no great name for this one.
34:05The Canadian Ontario Wayland trial.
34:07Depending on who you're talking about.
34:09I learned from this.
34:10I need to have make sure that any
34:13trials I have have a have a catchy name,
34:16but the start a trial and start be
34:18were done in England and the obviously
34:21the Canadian trial was done in Canada.
34:23They all compared their moderately
34:25hypofractionated regimens in whole
34:26breast radiation therapy to the standard
34:28conventional fractionation of welding.
34:29I guess we're going to call that conventional
34:32'cause modern hypo frack is now standard,
34:35but 50 Gray in 25 fractions was the
34:37standard arm and all Childs found
34:40no significant difference in local
34:42regional recurrence and overall
34:45survival for the patients.
34:47At 10 years they did all use a slightly
34:50different fractionation scheme to start.
34:53A trial,
34:54had had patients receiving 41.6 Gray or
34:5739 Gray and 13 fractions over 5 weeks,
35:01which is approximately 3 fractions per week.
35:04It's a little bit of.
35:06More challenging regimen to schedule,
35:08so most institutions are not
35:10really using this regiment,
35:11but it is interesting that they did.
35:14Note that a significant significant
35:16decrease in the number of patients
35:18with breast induration adima intellect
35:21until inject ages in the 39 Gray
35:23arm compared to the standard frac.
35:25The 41.6 Gray arm did not really
35:28do any better as far as then the 50
35:31Gray arm as far as acute effects
35:34an late term effects as that.
35:37Start B, which is what Yale is using.
35:40That's the 50 Gray and 15 fractions.
35:42So once a day Monday through Friday,
35:45that's three weeks.
35:46So once again their outcomes,
35:47local region of occurrence,
35:49overall survival at 10 years
35:51was the same with the 50 Gray,
35:53and there was a significant
35:55decrease in breast shrinkage,
35:56breast edema and telangiectasia.
35:58But age is in the 40 great arm.
36:01The Canadian trial was interesting.
36:03That is slightly different.
36:0442.5 in 16 fractions,
36:06so that's three weeks and a day.
36:10Subgroup analysis it's worthy
36:12of note that they did notice
36:14increased local regional recurrence.
36:16In high grade tumors,
36:18with the Hypo frac with 15.6% of
36:21patients who received with with high
36:24grade tumors that had hypo fact
36:27experience in local regional recurrence
36:29versus 4.7 in the 50 Gray arm.
36:32However,
36:33I will say that start B did look
36:35at that and did not find any any
36:39difference in outcomes for the
36:41Grade 3 tumors,
36:42so we tend to still treat those patients
36:45with moderate hypofractionation
36:46an in the Canadian trial,
36:48there was no significant difference
36:51in acute toxicity or cosmetic outcome.
36:54So maybe we can tighten things up
36:56a little bit more now and the newer
36:58regimens that are being brought out
37:01there are now called Ultra Hypofractionation.
37:03And these once again are in for the
37:06setting of whole breast radiation only.
37:08We are not yet talking about
37:11anything with the nodes.
37:13And we have two regiments,
37:15the fast regimen and the
37:17Fast forward regimen.
37:18Yale has adopted the FAST regimen which
37:20we've been using with great success.
37:23We've been very happy with it.
37:25We started using it in the fall of last year,
37:29so in the fast trial.
37:31Patients were randomized to one fraction
37:34of radiation per week to a total of
37:3828.5 Gray or to a total of 30 Gray,
37:41so that's 5.7 or 6 Gray once a
37:43week versus the more traditional
37:4650 Gray in the 25 fractions.
37:48This fast trial is randomized.
37:50It's well done,
37:52and it has 10 years of follow
37:55up at this point,
37:56and there was no significant difference
37:59in normal tissue affects in the 28.5 by
38:03ARM compared to the standard fractionation.
38:05And that's why I put that in.
38:07Read up there because that is really the arm
38:10that we are treating on in the 28.5 Gray arm,
38:13because the 30 Gray arm did have
38:15increase in normal tissue effects,
38:17so we're not using that.
38:19For all three dosing fractionation schemes,
38:21however,
38:21local regional recurrence,
38:23distant recurrence,
38:23and overall survival were equivalent,
38:25and this regimen has made it
38:28into the national guidelines.
38:29Now the NCC N guidelines saying
38:31that it may be considered for
38:33patients greater than 50 years of
38:36age with early stage breast cancer,
38:39which they have defined as as
38:41insight to T1T 2AN OI kind of put
38:44in that who do not require a boost,
38:47they had a few sentences about how boosted.
38:50Difficult in this setting and
38:52hasn't been established,
38:53but that's really how we
38:55are approaching it at Yale.
38:56If we have a patient with early stage
38:59cancer who does not require a boost,
39:01and we're not quite ready for patients
39:04as young as 50 with just such a
39:06short term follow-up of 10 years,
39:08so we are tending to lean
39:11towards patients 65 and over.
39:13Although if someone did have a a
39:16needed transportation need or something
39:18that still fit this requirement,
39:20we would be open for that.
39:22The Fast forward has not.
39:24It is not yet widely adopted because
39:27the data is only going out for five
39:31years at this point and that is
39:34looking at 26 or 27 Gray in five
39:37fractions just Monday through Friday.
39:39You're done in a week versus
39:41the what's now the more modern.
39:44Standard,
39:44then the modern standard hypo fractionation,
39:4740 Gray, and in 15 fractions.
39:49The five year data is promising.
39:51It's showing non inferiority
39:53and local control.
39:54There are increased normal tissue
39:56affects with the 27 Gray arm.
39:58So overtime I think we're going
40:01to be very interesting to see what
40:03happens with that 26 Gray arm.
40:05And if we get more data,
40:08more longer term data under our belt,
40:10that may be something that
40:12we will be adopting.
40:14In the future,
40:15that would certainly be very convenient.
40:20So, so far we've only talked about
40:23using the HYPOFRACTIONATION in settings
40:26where just the breast is being treated.
40:28What about in the setting of
40:31regional nodal or radiation,
40:33or post mastectomy radiation therapy?
40:35There is a growing body of maturing
40:38data and accruing data in this
40:40setting that we may see in the future
40:43that we are more widely adopting.
40:46The hypo fractionation for
40:48these patients as well.
40:49One trial that's ongoing right
40:52now is the RT charm trial.
40:54And it's looking at moderately
40:57hypofractionated post mastectomy
40:58radiation therapy for patients who've
41:01had breast reconstruction comparing
41:03with the standard 50 Gray and patients
41:06can have autologous reconstruction
41:09implant reconstruction immediate
41:10or delayed to be on this trial.
41:15The fabric trial that is open at
41:18Yale Dr Mina Moran is RPI for that.
41:22That's the study of radiation
41:24fractionation on patient outcomes
41:26after breast reconstruction
41:27for invasive breast cancer,
41:29and this is randomized as
41:32well to hypofractionation.
41:33Plus,
41:33the more standard 50 Gray and
41:36patience for this would have
41:38permanent implant or tissue expander.
41:41This is not for autologous patients.
41:43There is some published data.
41:46That one can find,
41:47for example,
41:48this trial out of China by Doctor Wang.
41:51It's a randomized trial of standard
41:54fractionation versus moderately
41:55hypofractionated patients in post
41:57mastectomy radiation therapy.
41:58I read every word in the article.
42:00I can find nothing that really
42:03discuss is if reconstruction was
42:05used and the median follow-up
42:07is not that long at 58.5 months,
42:09but there is an.
42:11These were a little bit high.
42:13These were some high risk patients as well.
42:17Four or more involved nodes
42:18for everybody T3T4,
42:20but there was no difference in local
42:22regional recurrence between the 50
42:24Gray in the moderate hypofractionation,
42:26but there was an increase
42:27in grade 3 acute toxicity,
42:29in the Hypo frac arm,
42:31so none of this has really LED for
42:33wide adoption of the of hypo frack in
42:36the setting of treating regional nodes
42:38or post mastectomy radiation therapy.
42:41At this point I have done
42:43it in very select patients.
42:45I think that the rest of our.
42:47Group has but it has not yet been
42:50adopted by the NCC N due to the
42:52paucity of data at this point.
42:54Although overtime,
42:55I'm sure that charm and fabric will
42:57provide us with a lot of information.
43:02OK. So, another way,
43:05besides shortening the treatment course
43:07in the number of visits is by decreasing
43:10the volume of tissue that we are treating.
43:13One way that's been around for awhile.
43:16Actually, you post all probably know,
43:18is accelerated partial breast
43:20irradiation therapy,
43:20and until recently there was a
43:22lack of longer term phase.
43:24Should say phase three up there
43:27scuse me of longer term phase
43:30three data supporting a PBI.
43:32We do have these two studies that I put
43:35up here that now are have randomized
43:38data giving us their ten year outcomes.
43:41The NSA BP.
43:4239 that looked at whole breast
43:44irradiation with standard frack versus
43:47accelerated partial breast irradiation
43:49therapy using either breakey therapy or
43:51external beam twice a day for 10 fractions.
43:54So patients would be done in a week.
43:57It's very interesting results,
43:59so they were really looking
44:01at in ipsilateral.
44:02Breast tumor recurrence.
44:03At 10 years it was found to be
44:074% and the accelerated partial
44:08breast irradiation and 3% in the
44:11whole rest of radiation arm.
44:13But based on their statistical analysis,
44:15even though there's just that 1% difference,
44:18it did not meet the criteria for equivalence,
44:21so API was not bound to be equivalent
44:24to whole breast or radiation therapy.
44:27That being said,
44:28in the discussion the authors
44:30discuss how with that 1% difference
44:32in lower risk patients.
44:34This still does perhaps leave the door
44:37open for a PBI for for low risk patients.
44:41The Florence trial.
44:42He has gained a lot of attention
44:44and that has treated accelerated
44:46partial breast irradiation therapy.
44:48So when we're trading with accelerated
44:50partial breast radiation therapy,
44:51you probably all know that we are really
44:54concentrating the radiation therapy
44:56on the tumor bed and an expansion,
44:59and therefore we are leaving
45:00more of the well.
45:02We're leaving the uninvolved breast
45:04or a good portion of the uninvolved
45:07rest out of the high dose area.
45:09And by tightening our fields
45:11like this one can.
45:12Also.
45:15Less dose to the healthy tissues as well,
45:19so the Florence trial used accelerated
45:21partial breast radiation therapy
45:2330 Gray and five fractions using
45:25and I MRT approach versus whole
45:27breast and standard fractionation.
45:29So at 10 years with their randomized trial,
45:33there was no significant difference in
45:35ipsilateral breast tumor recurrence.
45:37It was 2.5% in the whole breast
45:40versus 3.7% in the accelerated
45:42partial breast irradiation therapy.
45:43But based on their statistical analysis,
45:46this was not.
45:47Statistically different,
45:48there was also significantly less
45:50acute in late term toxicity with the
45:53accelerated partial breast radiation therapy,
45:55so they partial breast irradiation therapy
45:58has made it into the national guidelines.
46:01It's been there for a little while,
46:04but on the most recent iteration,
46:07the Florence Regiment is listed
46:09as the preferred regimen,
46:11and it is recommended that the
46:14Astro guidelines where I've put
46:16a reference on here.
46:18As many of you may know,
46:21Astro has published guidelines regarding
46:23who is suitable for accelerated
46:26partial breast irradiation therapy,
46:28and there are three groups,
46:31suitable cautionary and basically
46:33do not treat unsuitable.
46:36So here at Yale, we are working.
46:39We do treat accelerated partial
46:41breast irradiation therapy.
46:42Although not very often for suitable cases,
46:45just because the hypo frack is so
46:47works out so well and you're really
46:50not saving the patient much time.
46:52However, we are in the process
46:54of gearing up to start offering
46:57treatment in the manner that
46:58was used in the Florence trial,
47:01the 6th grade Perfection Times 5
47:03fractions and that was every other day.
47:06Using I MRT.
47:07So we are working with our physics
47:09department and doing all the safety
47:11checks and getting our policies and
47:13procedures in place to start adopting that.
47:15But we are not on line for that just yet.
47:21So what about decreasing our the
47:24amount of tissue that's treated in the
47:27setting of regional nodal irradiation?
47:30Well, there is some ongoing trials that
47:33we read before this is widely adopted
47:35to start eliminating our nodal fields.
47:38In certain cases we need some
47:40more guidance on that in,
47:42especially in the post mastectomy
47:44setting you know who who,
47:46when the patients have involved,
47:48knows, who can we really skip treating
47:50the regional nodes and still ensure
47:53that we have excellent outcomes?
47:55This trial, the NSA BP 51 it was
47:58open at Yale for a while and it
48:01was very challenging to accrue to,
48:04and it was nationally quite difficult to
48:07accrue too so really long trial may not name.
48:11Maybe that was part of it that it's a bait.
48:15You can read the name there,
48:17but basically what it does is it
48:19took patients who had pathologically
48:22proven by biopsy,
48:23axillary nodal involvement who received.
48:25Neoadjuvant chemotherapy.
48:26Then they would undergo either
48:29lumpectomy or mastectomy.
48:30And they could have Sentinel
48:33lymph node biopsy,
48:34Sentinel lymph node biopsy converted
48:36to XI section or XI section.
48:39But if they were converted to YPN 0
48:43then these patients were eligible.
48:46Remember,
48:46they had to have T1T3 pathologically
48:49proven N1 disease upfront,
48:51neoadjuvant, chemo,
48:52and then rendered YPNO in the axilla.
48:56So arm one was omission of
48:58regional nodal irradiation therapy,
49:00with so lumpectomy patients would only
49:02have the breast treated high tangents.
49:05Not allowed.
49:06Mastectomy would have no radiation.
49:08An arm two,
49:09which was I call it the yes regional
49:11nodal radiation therapy would treat
49:14in though that arm the whole breast
49:17and the chest wall would receive
49:20radiation plus regional nodal
49:22irradiation which was defined on
49:24the trial as internal mammary nodes.
49:27Une dissected axilla.
49:30And the superclass.
49:30So you're either getting a very
49:32limited radiation or basically the full boat.
49:34And I think that some people
49:36when I mean I know when I talk
49:38to patients about the trial one,
49:40either want they either
49:41wanted one arm or the other,
49:43and many people were reluctant to let go
49:45of the regional nodal radiation therapy.
49:47So I personally was not able to accrue
49:50anyone to the trial when I spoke with them.
49:52And I think that that was a
49:54problem kind of nationwide,
49:56but it's now closed to accrual.
49:57They've obviously reached their goal,
49:59which is great.
50:00And I am not aware of any
50:03preliminary results at this time.
50:06Another trial this is open at
50:09Yale and we are actively accruing.
50:11So please we would love to have
50:14your patience on this trial.
50:16The MA 39 also called Taylor RT.
50:19This is different.
50:20This is not really looking at
50:22response to chemotherapy.
50:24It is looking at omitting regional
50:26nodal radiation therapy for patients
50:28who have a more favorable cancer as
50:31far as biomarker risk is concerned.
50:33So the and the inclusion criteria.
50:36Changed extremely recently within
50:37the last eight weeks.
50:39Initially when we open the trial,
50:41only T1 or T2 patients were
50:43allowed on the trial,
50:45but now patients with T3 disease are allowed.
50:48Also, a very recent change and what the
50:51definition of low volume nodal disease.
50:53What is this? Is the updated version here,
50:56so if the patient had lumpectomy
50:58or mastectomy an axe dissection,
51:00they can have one to three positive
51:02nodes if they have lumpectomy
51:04or mastectomy plus Sentinel.
51:06Lymph node biopsy only.
51:07They can now have one to two positive nodes.
51:10That's a change.
51:11And a huge change is that the archetype
51:14score when this trial opened had to
51:17be 17 or less to enroll patients.
51:21Now patients with an archetype score
51:23of 25 or less our are eligible.
51:26They cannot have had neoadjuvant
51:28chemotherapy.
51:28They've also made it amendment allowing
51:31for they are allowing for neoadjuvant.
51:33I should have said Neo there,
51:36excuse me.
51:37Neoadjuvant endocrine therapy is now allowed.
51:41Agement chimos allowed.
51:42Agement endocrine therapy is allowed.
51:44Patients are randomized,
51:45similar to the other one.
51:47The no regional nodal radiation
51:49arm that no RNI,
51:51so those patients would have to have whole
51:54breast irradiation if they had lumpectomy,
51:56but no radiation.
51:57If mastectomy and then yes,
51:59are in,
52:00I would be whole breast irradiation
52:02or chest wall irradiation depending
52:04on their surgery and regional nodal.
52:07And like the other trial,
52:09regional nodal means internal mammary nodes.
52:11Une dissected axela in the superclass.
52:15And the primary endpoint is breast
52:17cancer recurrence free interval,
52:19but of course they're over looking at.
52:22You know, local recurrence,
52:24distant recurrence, side effects,
52:25and lymphoedema risk as well.
52:30So the last way to limit or deescalate the
52:34radiation therapy is to just not do it.
52:37That's the kind of most straightforward.
52:39I think that a lot of us now are
52:42familiar with the CL GB 9343 trial.
52:45I can, you know,
52:47memorize this one in my sleep.
52:49Those patients were 70 years
52:51of age or older T1 tumors.
52:53They could be clinically or
52:55pathologically node negative had
52:56to be hormone receptor positive and
52:59lumpectomy with negative margins.
53:01I put the negative margins in red
53:03because for this trial negative
53:05margins was defined as no tumor on Inc.
53:09The patients were randomized to
53:11tamoxifen alone or whole breasts or
53:13radiation therapy using a moderate
53:16hypofractionation course plus tamoxifen.
53:18At 10 years you could see the overall
53:21survival was the same 67% in Tamar T
53:24and 66% in the Tam arm with a lot of
53:28those deaths being non breast cancer
53:30deaths and freedom from local regional
53:33recurrence was 98% in the Tamar TR man,
53:3790% in the Tamar that actually
53:39was statistically significant,
53:40there was a statistically significant
53:42reduction in the risk of local regional
53:45occurrence with the radiation being provided.
53:48So you might say, well,
53:50this trial should support us doing
53:52the radiation,
53:53but because the overall survival
53:55was not different and although
53:57I don't have it up there,
53:59the very low rate of distant
54:01recurrence was no different.
54:02The breast cancer specific
54:04mortality was not different,
54:05so the radiation was not doing
54:07anything to prevent those more.
54:09One could argue more meaningful outcomes.
54:11So this could.
54:12This is used for two in support
54:14of omitting radiation therapy for
54:17women that meet the criteria.
54:19If I see patients and I have a 71
54:21year old patient who is very who I
54:24feel has a life expectancy exceeding
54:2610 years or then we talk about hey,
54:29maybe we should do the radiation so.
54:32But it is good fodder for discussion
54:34and an it can help to find those
54:37patients for whom a mission of radiation
54:40therapy would be certainly acceptable.
54:42Also,
54:43patients are not going to
54:44take the endocrine therpay.
54:46They really should get the radiation.
54:48Prime two is similar.
54:50It's a little bit behind as far
54:52as how long it's been accruing
54:54and following out the data.
54:56The women can be 65 or older,
54:59T2 tumors up to three CM.
55:01They must have pathologically
55:03negative nodes with Sentinel node
55:04biopsy or XI section hormone receptor
55:07positive and their definition of a
55:09negative margin is 1 millimeter.
55:10They live had some limits that
55:13the CL GB trial did not.
55:15The tumor could be grade 3 or have elvii,
55:18but you could not have.
55:20Both an once again must have
55:22adequate their Bay and we see
55:24similar results at the five years.
55:26It almost mirrored the CLG be at
55:28the five years where ipsilateral
55:30breast tumor recurrence was around
55:321% in the radiation arm and 4%
55:35in the no radiation arm with no
55:37difference in overall survival.
55:39There was a recent update
55:40at the San Antonio Breast
55:42Conference, however, that paper has
55:44not followed showing similar results
55:46as CLG be at 10 years with ipsilateral
55:49breast tumor recurrence around 10.
55:51In the know in the, I miss those up in
55:55the no RT arm and then .9% in the RT arm.
55:58So I think that Prime 2 once
56:01that paper comes out,
56:03you know we may start offering for younger
56:06women or women with some larger tumors.
56:08Omission of radiation therapy.
56:11Now this is my last slide before I get
56:14into the thank yous in the summaries,
56:17and these are trials that
56:18I'm not that familiar with.
56:20To be frank with you,
56:22there seemed to be more surgical trials,
56:24but I thought they were worth
56:26just springing up.
56:27We have the comet trial open at Yale.
56:30The Pi is doctor Golshan,
56:31and that if I'm understanding correctly,
56:33looks at.
56:34You know what's considered a lower
56:36risk DCIS grade one and grade two and
56:39looking at endocrine therapy alone
56:40with surveillance in lieu of surgery,
56:42an obviously,
56:43if we don't do surgery.
56:45We're not coming to the radiation,
56:47so in a way this would be part of
56:49omitting radiation and the Lord
56:51trial is somewhat similar as well.
56:53I'm for my homework.
56:54I feel I need to learn a little
56:56bit more about these trials,
56:58so I'll give you guys some homework too,
57:01but I felt that it would not be
57:03complete without bringing it up,
57:05but I think it's interesting
57:06you know the question that seems
57:08to be being asked if I'm is,
57:10can screen detected low risk
57:11DCIS be managed by an active
57:13surveillance strategy rather than.
57:15Surgery.
57:15So in summary,
57:16we are seeing you know in real
57:19time and working further towards a
57:22deescalation of radiation therapy for
57:24appropriate patients in regard to
57:26the number of treatment visits infractions,
57:29the volume of tissue treated,
57:31and the appropriate emission
57:32of radiation therapy,
57:33and I'd like to thank you if you
57:36have any questions about any of the
57:38references or would like to discuss further.
57:42That's my contact info,
57:44thanks.
57:45Thank
57:45you so much Doctor Knowlton wow
57:47three really fantastic talks and I
57:50really appreciate everyone's time and
57:51effort in our audience for listening
57:54and putting in some questions.
57:56Please feel free to put in.
57:58More questions will be happy to answer
58:01them and while we wait for those I have
58:04a couple just listening to the talks.
58:06Maybe I'll start with Doctor, Doctor
58:09Hooley and a little bit about the contrast.
58:12Enhance image Ng for screening and
58:14how you can do that without contrast.
58:16Potentially I was.
58:20You know like more,
58:21but you know you know where we're
58:24at in the United States and maybe
58:27where we're going and
58:28be great to hear about that.
58:31Sure, so uh, MRI has shown that
58:33contrast enhanced screening has the
58:36highest cancer detection rate, right?
58:38So because cancers are vascular,
58:40and so you know,
58:41that's the way it's going with contrast,
58:44enhanced mammography,
58:45and even like in the breast
58:48imaging which all require.
58:49You know Ivy contrast.
58:51There are some studies looking at
58:53MRI and diffusion weighted images,
58:56or some people who say that
58:58they will never happen.
59:00Some people say that it will
59:03perhaps somehow happen that you
59:05could do MRI with diffusion,
59:07weighted imaging or some other technique
59:10that some really smart people are
59:12going to invent and figure out some
59:15some sequences where we can look at
59:18vascularity without Ivy contrast injection.
59:20Likewise, there are also some
59:23ultrasound products out there.
59:25Randy Butler participated in
59:27an auto acoustics ultrasound
59:29study that was the optoacoustic.
59:32Ultrasound equipment was just
59:33FDA approved last January and
59:36it's basically looking at heating
59:38lasers and heating lights.
59:40Laser light and heating the blood
59:43vessels and looking determining
59:45oxygenation within the blood vessels.
59:48And she published a couple of articles.
59:51Common radiology,
59:52which is our top journal showing
59:54the vascularity within tumors
59:56and superimposing that over a
59:58traditional ultrasound so that
60:00is vascular based without without
01:00:01contrast and there's some other.
01:00:05New ultrasound techniques.
01:00:06Also that are a little bit
01:00:08different that measure.
01:00:09They can measure vascularity as well,
01:00:11so those are the ones that right now are.
01:00:16Active you know, and we could see it.
01:00:18You know,
01:00:18in five or ten years or maybe sooner.
01:00:20Who knows.
01:00:21Well,
01:00:21actually opt acoustics is already out there,
01:00:23so you have to wear fancy
01:00:25space classes and stuff.
01:00:27Awesome,
01:00:27thank you a question for Doctor Abraham.
01:00:30What are some of the signs or
01:00:32indications that you know clinicians
01:00:34out there should be aware of,
01:00:37for you know for those that end up
01:00:39getting implants for reconstruction
01:00:41with the implant associated anaplastic
01:00:43large cell lymphoma, which is, you know,
01:00:47gotten some press in the last year or two.
01:00:51Dial yeah, so first of all the the presence
01:00:54of a textured implant which is obviously
01:00:56for somebody who's not a plastic surgeon.
01:00:59Maybe a little bit challenging.
01:01:01So if there's any concern you know,
01:01:03have the patient go back to the plastic
01:01:05surgeon so you know because we are at
01:01:08this point considering removing them
01:01:10sort of prophylactically and then any change,
01:01:13particularly a delayed ceroma,
01:01:14is what is classically referred to.
01:01:16So you know in in breast surgery
01:01:18seromas are not uncommon,
01:01:20but you know, at the time of
01:01:22surgery or immediately following.
01:01:24Postmastectomy radiation,
01:01:25but if there is a saroma that develops
01:01:30and delayed fashion to 310 years after an
01:01:33implant is placed at sign for concern.
01:01:36Thank you and maybe a last question.
01:01:39For doctor Knowlton.
01:01:40You know, I I,
01:01:41you know,
01:01:42often we see patients that are over
01:01:44the age of 70 small your positive
01:01:47breast cancers and you know with
01:01:49the LGB data that you showed you
01:01:52know undergoing breast conservation
01:01:53and forgoing radiation and you
01:01:55know doing anti estrogen therapy.
01:01:57But have you also seen the converse
01:01:59where some would just prefer to do a
01:02:01short course of radiation as opposed
01:02:03to putting themselves through?
01:02:05You know 5 plus years of anti
01:02:08estrogen therapy.
01:02:09I guess like if we bias a patient one
01:02:12way or the other when they get to you,
01:02:14how is that
01:02:15discussion go that I see this every week?
01:02:18I would say every week.
01:02:19So and you know, I listen to the patient.
01:02:22Many of them come in with some biases
01:02:25against the endocrine therapy.
01:02:27So that doctor Google doesn't do
01:02:30endocrine therapy much justice.
01:02:31So I talked to them about data showing
01:02:34that you know at least half of
01:02:36patients really don't get any of these.
01:02:39You know, join aches or hot
01:02:41flashes and that's placebo.
01:02:42Patients got the same amount.
01:02:44Maybe they should just give it a try.
01:02:47I discussed the benefit of helping prevent
01:02:49breast cancer in the contralateral breast.
01:02:52An IV after I finish my spiel,
01:02:54it's attempting to get them to be
01:02:57more open to AI or.
01:02:59Tim, sometimes they will try it
01:03:00and we'll check back in with each
01:03:03other in two to three months.
01:03:04And if they're still taking it in,
01:03:06tolerating it super,
01:03:07or if they're not,
01:03:08then I have come back and done the
01:03:11radiation at that point or even,
01:03:12or some if they might give my
01:03:15initials feel an they still tell
01:03:17me I'm not by I'm not going to
01:03:19take it no matter what I say, OK,
01:03:21I hear you and then we would either.
01:03:23Do you know?
01:03:24Depending on the characteristics of the
01:03:26tumor and the patients comorbidities,
01:03:28we may do a fast regimen of once a week,
01:03:31or you may do the moderately hypo frack.
01:03:33The 15.
01:03:34Plus or minus a boost,
01:03:35so I certainly do see that that
01:03:37quite quite often every week.
01:03:40Ann and maybe just to finish off on on
01:03:42that when they you said maybe try anti
01:03:45estrogen therapy for a month or two.
01:03:47Is there kind of a cut off where you
01:03:50would say that if they went with
01:03:52anti estrogen and decided to stop
01:03:54and wanted to come back to you to
01:03:56radiation where you'd feel comfortable.
01:03:59Well, that's a good question.
01:04:00You know two or three months
01:04:02I wouldn't even blink an eye,
01:04:04especially if they were taking
01:04:05endocrine therapy for the bulk of
01:04:08that I have done up to six months.
01:04:09I have done it, but at that point we
01:04:12may ask the patient to have another
01:04:14Mamo before starting the radiation.
01:04:16And sometimes I'll bring those patients
01:04:18up in our multidisciplinary tumor board.
01:04:19I did have one patient where it was a
01:04:22year out, but she was substantially high.
01:04:24Risk enough that I presented,
01:04:26or at our multidisciplinary
01:04:27tumor board we got.
01:04:29Breast imaging no evidence that not.
01:04:31There's nothing suspicious on that,
01:04:33and I did offer radiation,
01:04:34but beyond six months I would really
01:04:36want to have a multidisciplinary
01:04:38discussion about that.
01:04:41Thank you and again thank you all
01:04:43so much for these three wonderful
01:04:45presentations I I learned so much
01:04:47in the course of the last hour and
01:04:50a half and the great thing is that
01:04:52this is recorded so others could go
01:04:54back and be able to look at that.
01:04:57Really thank the audience for
01:04:58joining us for this series of three
01:05:00breast CME's here at Yale and and
01:05:02look forward to continuing them
01:05:04in the next academic year.
01:05:06So with that thank you so much.
01:05:08Have a great weekend. Thank
01:05:09you, thank you.