MolDX: Biomarker Risk Stratification Testing in DCIS Contractor Advisory Committee (CAC) Meeting Transcript - July 15, 2024 - JF Part A
MolDX: Biomarker Risk Stratification Testing in DCIS Contractor Advisory Committee (CAC) Meeting Transcript - July 15, 2024
Note: The recording of the MolDX: Biomarker Risk Stratification Testing in DCIS CAC Meeting is available on the PalmettoGBA YouTube channel.
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Gabriel Bien-Willner
Have a little you let me know when it's started.
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Evelyn Etidau
It's recording.
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Gabriel Bien-Willner
OK, great.
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Gabriel Bien-Willner
I'm gonna make a subsequent announcement.
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Gabriel Bien-Willner
Uh, yeah, that I just mentioned that we would be recording this meeting and I have just started the recording of this contractor Advisory Committee meeting in compliance with CMS for the record prior to doing so.
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Gabriel Bien-Willner
I announced that Palmetto GBA would be making an audio recording of the CAC meeting and consented on behalf of Palmetto GBA. On other side.
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Gabriel Bien-Willner
Thank you very much for those of you that have joined us.
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Gabriel Bien-Willner
I know there's a lot of people on the call I want to first make a couple of announcements.
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Gabriel Bien-Willner
One is we got a lot of interest and participation of this meeting.
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Gabriel Bien-Willner
The goal of this meeting is to discuss translation practice at evidence, etcetera in a in a discussion, and unfortunately we could not accommodate everybody who wanted to participate.
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Gabriel Bien-Willner
We had approximate or over 20 people who wanted to participate in this and I just felt that that would make it difficult to have an active conversation with too many people in the room.
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Gabriel Bien-Willner
That said, if you're on this call and have evidentiary information that's pertinent to the discussion that isn't discussed, it would like to send that to us.
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Gabriel Bien-Willner
You may do so.
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Gabriel Bien-Willner
Umm.
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Gabriel Bien-Willner
Thought I'd start off by first introducing myself.
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Gabriel Bien-Willner
My name is Dr. Gabriel Bien-Willner, I am and the director of the MoIDX program, Palmetto GBA.
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Gabriel Bien-Willner
The MoIDX program is a joint operation between four Medicare administrative contractors that all should be participating in this call or present on this call.
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Gabriel Bien-Willner
That includes not just Palmetto GBA but also Noridian, WPS, and CGS.
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Gabriel Bien-Willner
The representatives of those contractors will also be present and the Policy that's derived from this engagement or that this engagement is relevant to umm, would ultimately be in a shared Policy between all those contractors as we share such policies.
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Gabriel Bien-Willner
We put this task together.
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Gabriel Bien-Willner
Because there are requests for Policy in this space and in the review of the evidence, it became clear to us that there was Information, uh, that we needed to discuss with experts in the field.
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Gabriel Bien-Willner
We want to write Policy.
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Gabriel Bien-Willner
I'll make this clear.
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Gabriel Bien-Willner
Our goal is to write policy, the best possible policy we can that considers the most accurate evidence that's available.
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Gabriel Bien-Willner
Uh to determine whether services meet the threshold of reasonable and necessary and for us to do so in the diagnostic space we consider whether services have demonstrated analytical validity, clinical validity, and clinical utility.
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Gabriel Bien-Willner
And it became apparent to us we needed additional information from experts to determine particularly the clinical validity and clinical utility questions.
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Gabriel Bien-Willner
And to that end, we proposed a series of questions that help us understand in a systematic way to make that determination.
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Gabriel Bien-Willner
The evidentiary support for these kinds of services in consideration of how do physicians make decisions relevant to these services, what are the important considerations?
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Gabriel Bien-Willner
What are the important variables that not only change management decisions but can also improve patient outcomes, which is really the standard?
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Gabriel Bien-Willner
So that's said, I thought the next I would like to have the panel, umm, introduce themselves.
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Gabriel Bien-Willner
I let me make sure I could see everybody who's present here.
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Gabriel Bien-Willner
I'm gonna, if you don't mind.
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Gabriel Bien-Willner
Panel members.
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Gabriel Bien-Willner
I'm going to call you and just the order that I have listed uh on the separate list here, but if you could introduce yourself and you provide your affiliation or just general background quickly and that's this will also help us test to make sure that the microphones and everything is working appropriately.
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Gabriel Bien-Willner
I'm.
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Gabriel Bien-Willner
I'm gonna start with Doctor Eileen Connolly if you're available.
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Gabriel Bien-Willner
I see your arm and I and I see you're muted.
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Gabriel Bien-Willner
See if you can unmute yourself please.
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Eileen P. Connolly
OK.
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Eileen P. Connolly
Thank you.
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Eileen P. Connolly
Sorry, that helps this.
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Eileen P, Connolly
I'm Eileen Conley.
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Eileen P. Connolly
I'm a radiation oncologist at Columbia University.
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Eileen P. Connolly
Just keep it brief.
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Gabriel Bien-Willner
Thank you very much, Doctor Kimberly Van Zee.
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Gabriel Bien-Willner
We're gonna be working through these technical issues and let's make sure we get you to be unmuted.
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Gabriel Bien-Willner
Doctor Van Zee, I believe I've unmuted you and you could unmute yourself if possible.
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Gabriel Bien-Willner
And if not, Evelyn, if you're the one who?
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Gabriel Bien-Willner
OK, there should be at the top of the screen.
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Gabriel Bien-Willner
There should be a couple of toggled icons.
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Gabriel Bien-Willner
One is camera, one is mic.
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Kimberly Van Zee
There.
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Gabriel Bien-Willner
I see that you there we go.
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Kimberly Van Zee
Got it.
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Kimberly Van Zee
I got it.
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Kimberly Van Zee
Kimberly Van Zee, I'm a breast cancer surgeon at Memorial Sloan Kettering.
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Gabriel Bien-Willner
Thank you very much.
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Gabriel Bien-Willner
Alright.
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Gabriel Bien-Willner
Doctor Atif Khan.
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Gabriel Bien-Willner
And by the way, when I when I call your name, I have to find you on this list and manually.
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Gabriel Bien-Willner
Uh on turn on your mic and then you have to go and see if you can if you can toggle it on.
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Gabriel Bien-Willner
Umm, Dr.
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Atif Khan
OK.
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Atif Khan
Yeah, I'm.
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Atif Khan
Can you hear me now?
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Gabriel Bien-Willner
Yes, we can.
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Atif Khan
OK, perfect.
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Atif Khan
Uh.
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Atif Khan
Atif Khan, a radiation oncologist I lead the breast radiation oncology group at Memorial Sloan Kettering Cancer Center.
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Gabriel Bien-Willner
Thank you. Doctor Kahn.
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Gabriel Bien-Willner
Next will be Doctor John Williams and give me a second here.
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Gabriel Bien-Willner
And make sure I turned you on. OK.
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Gabriel Bien-Willner
There you should be able to unmute yourself.
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John Williams
Thank you.
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John Williams
John Williams.
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John Williams
I'm a breast cancer surgeon in private practice in Northern Virginia.
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John Williams
I chaired the President's Cancer panel, which advised the last two administrations on and the President on the National Cancer program.
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John Williams
I'm no longer on that panel.
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John Williams
I have no federal authority and I have no financial relationships with any Company.
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John Williams
One quick thing, why don't we turn on the video?
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John Williams
It might.
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John Williams
It helps with engagement and communications.
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John Williams
I feel very disconnected without the video.
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Gabriel Bien-Willner
Thanks, Dr. Williams.
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Gabriel Bien-Willner
That's a great question.
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Gabriel Bien-Willner
Let's see if we can do that.
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Gabriel Bien-Willner
I will ask Evelyn if she knows how to ensure that the cameras can be turned on, all I see is access.
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Gabriel Bien-Willner
No, I do see it for camera as well and then I will slowly but surely go through everybody and turn it on as well.
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Gabriel Bien-Willner
Sorry again for the.
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Gabriel Bien-Willner
For the trouble with the IT, that's always there's always something, but I'm going through the group and ensuring that everybody has the ability to turn on their cameras if they choose.
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John Williams
I thought it only affected us, not you guys in government.
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John Williams
Uh, the Verizon guy was in my house working on Internet.
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John Williams
Sorry to keep it, yeah.
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Gabriel Bien-Willner
That's no, uh, fortunately, we all have these kinds of problems.
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Gabriel Bien-Willner
I wish things work so well for us all the time.
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Gabriel Bien-Willner
All right, I've turned on the access to cameras to everyone who's spoken so far, I believe.
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Gabriel Bien-Willner
Hold on a second.
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Gabriel Bien-Willner
Dr. Kahn again in the next.
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Gabriel Bien-Willner
You've made it more complicated for me.
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Gabriel Bien-Willner
Now I have to turn on your camera and your microphone.
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Gabriel Bien-Willner
There we go.
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Gabriel Bien-Willner
OK, I'm gonna go to the next participant.
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Gabriel Bien-Willner
That's doctor Brian Cziernicki
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Gabriel Bien-Willner
And I apologize if I butchered your name.
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Gabriel Bien-Willner
I'm used to it, by the way, people butcher my name every day.
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Gabriel Bien-Willner
One second, let me get to you and make sure you're turned on.
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Gabriel Bien-Willner
You should be able to turn on your microphone and your camera.
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Gabriel Bien-Willner
At this point.
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Brian J. Czerniecki
Yeah, Brian Czerniecki
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Brian J. Czerniecki
I'm a chair of breast oncology at Moffitt Cancer Center in a breast cancer surgeon.
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Gabriel Bien-Willner
Thank you very much.
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Gabriel Bien-Willner
Next is Dr. Anne Peled.
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Gabriel Bien-Willner
I do not see it on the list here.
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Gabriel Bien-Willner
I will also, as I see them, be unmuting the participants on the government side as well.
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Gabriel Bien-Willner
Who?
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Gabriel Bien-Willner
Uh, for whatever reason, everybody's Mic got turned off, unfortunately.
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Gabriel Bien-Willner
Uh, Dr. Kahn, let me check on that camera for you.
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Gabriel Bien-Willner
And Dr. Peled, if you're on, if you could text me or make sure I see your name on here because I'm, I'm not finding it.
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Gabriel Bien-Willner
OK, doctor.
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Gabriel Bien-Willner
Connect your camera should be working now.
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Gabriel Bien-Willner
There we are.
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Gabriel Bien-Willner
Alright, we're gonna skip Dr. Peled for now.
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Gabriel Bien-Willner
And lastly, Dr. Alastair Thompson.
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Gabriel Bien-Willner
I also want to comment that we have over 100 attendees at this point.
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Gabriel Bien-Willner
Oh, I see you.
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Gabriel Bien-Willner
Thank you for making sure you're letting me know that you're here.
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Gabriel Bien-Willner
I'll make sure I have to find your name on the list of participants so that I can make sure you are.
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Gabriel Bien-Willner
You're turned on here.
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Gabriel Bien-Willner
Give me a second.
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Gabriel Bien-Willner
Here you are.
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Gabriel Bien-Willner
Alright, Dr. Thompson, you should be able to speak now.
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Gabriel Bien-Willner
And I'm gonna also enable your camera is also enabled.
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Alastair Thompson
Thanks so much.
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Alastair Thompson
My name is Alistair Thompson.
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Alastair Thompson
I'm a surgeon in Houston, at Baylor College of Medicine.
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Alastair Thompson
Very involved nationally and internationally and clinical trials, clinical studies.
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Alastair Thompson
Thank you for letting me join you.
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Gabriel Bien-Willner
Thank you.
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Gabriel Bien-Willner
So we've heard from everybody who, uh, I wanted to keep the group relatively small so we could all have more intimate conversations.
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Gabriel Bien-Willner
Looks like we may have lost Dr. Peled.
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Gabriel Bien-Willner
Uh.
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Gabriel Bien-Willner
And if she's on, please send a text so that we can make sure that you're able to speak umm, I want to reiterate again.
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Gabriel Bien-Willner
The point is to have a conversation.
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Gabriel Bien-Willner
It's for us to understand the evidence as it is the practice decision making as it currently exists and also with the evidence supports of how it should exist.
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Gabriel Bien-Willner
You'll notice that the questions are written in such a way for us to.
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Gabriel Bien-Willner
You wise, logical fashion try to understand the decision making so that we can apply a logical framework of determining reasonable and necessary.
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Gabriel Bien-Willner
Umm.
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Gabriel Bien-Willner
As objectively as possible, with the evidence that exists.
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Gabriel Bien-Willner
So with that, I wanted to just start off by just posing the question and allowing the participants to speak to these questions as they like.
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Gabriel Bien-Willner
You don't have to raise your hand, just speak as in a conversational way to address the questions.
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Gabriel Bien-Willner
The first question being and all these questions, I will admit our you know multi part and may repeat the same question kind of in different ways to make sure we really understand from different perspectives how these things are considered.
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Gabriel Bien-Willner
The question is what clinical outcomes are considered relevant and breast ductal carcinoma, DCIS.
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Gabriel Bien-Willner
Uh, good for us ductal carcinoma inside, too.
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Gabriel Bien-Willner
I'm sorry, DCIS patients for use of radiation therapy and I'll use RT in the language here is the is the appropriate endpoint for consideration ipsilateral breast tumor recurrence, invasive cancer mortality or some other metric.
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Gabriel Bien-Willner
And the question is why?
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Gabriel Bien-Willner
Or is it a combination of these things and I'll let anyone who wants to address this speak up.
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Gabriel Bien-Willner
And I'll also say on the government side, anybody else any other medical directors are also free to chime in with any supplemental follow up questions if they have that interest.
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Alastair Thompson
Well, since there are defining silence or maybe start by suggesting that in breast recurrence and development of invasive cancer really are the key things that DCIS itself does not lead to mortality.
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Kimberly Van Zee
And I would add that if there were some way to identify the rare cases of breast cancer mortality from DCIS, which is admittedly very rare in the randomized studies, it's always in the low single digits.
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Kimberly Van Zee
But if there were, that would be obviously very important.
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Kimberly Van Zee
But it isn't, as Dr. Thompson just said.
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Kimberly Van Zee
So I think either in breast recurrence or invasive cancer is important and outcome endpoint obviously invasive is more important, but even just a DCIS recurrence has implications for woman's quality of life even if not quantity of life and need for therapy.
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Kimberly Van Zee
OK.
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Atif Khan
Yeah, I would echo all of what has been said by uh.
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Atif Khan
By Kim and Alistair, and I'll add that in the vein of, you know, additional treatment necessary and at least one report that I know of, the mastectomy free survival, was subsequent mastectomy, free survival was improved with the use of adjuvant radiotherapy versus not so.
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Atif Khan
So the that is also an implication or consideration.
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John Williams
One of the things that we're a little blind to is your experience with breast cancer and who's making these decisions.
0:17:6.535 --> 0:17:9.895
John Williams
And one of the critical things is to put into a larger context.
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John Williams
If you're not in the middle of the field and that one of that is that about 20% of patients that we categorize as breast cancer and DCIS is included in that, our DCIS and yes, in many ways, we tend to over treat it.
0:17:23.945 --> 0:17:48.115
John Williams
We treat it with surgery, radiation, sometimes some estrogen blocking medications for something that it's harm to you is small, but when it does develop into a cancer, it is a it is our job up front to prevent death from subsequent cancers and also prevent and do our best to prevent subsequent interventions that are needed that threaten patients.
0:17:48.125 --> 0:18:2.45
John Williams
So little bit of a background on that, but I would agree, invasive cancer currents and when they do recur locally, it's half and half DCIS half and half invasive cancer, correct me if I'm wrong.
0:18:2.55 --> 0:18:3.235
John Williams
We've got a great panel here.
0:18:3.245 --> 0:18:4.825
John Williams
There are more researchers than I.
0:18:4.895 --> 0:18:7.705
John Williams
I'm a little more Policy based in practice based just so you know.
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Gabriel Bien-Willner
Well, thank you for that.
0:18:12.135 --> 0:18:19.25
Gabriel Bien-Willner
For that information, if there's any other thoughts on this question, we can entertain them.
0:18:19.35 --> 0:18:21.945
Gabriel Bien-Willner
Otherwise, we can move on, but I will talk to Williams.
0:18:21.995 --> 0:18:40.235
Gabriel Bien-Willner
Address your question that people making this decision are a combination of many medical directors that are involved in the four contractors, and we have different levels and fields of expertise, expertise and experience.
0:18:40.635 --> 0:18:51.515
Gabriel Bien-Willner
I personally am a molecular genetic pathologist by training, anatomic pathologist by training umm and an expert in molecular diagnostics and have PhD in Human Genetics.
0:18:52.635 --> 0:18:59.755
Gabriel Bien-Willner
Uh, I've obviously ideal with cancer mostly, and rendering these kinds of services.
0:19:0.845 --> 0:19:9.85
Gabriel Bien-Willner
Umm, so from an analytical validity and clinical validity perspective, there's not much of a concern and understanding evidence that exists.
0:19:9.295 --> 0:19:11.645
Gabriel Bien-Willner
The concern is really the utility.
0:19:12.255 --> 0:19:15.585
Gabriel Bien-Willner
The concern is really how do you make decisions?
0:19:15.595 --> 0:19:16.645
Gabriel Bien-Willner
How should you?
0:19:16.715 --> 0:19:19.165
Gabriel Bien-Willner
Well, first, how should you be making decisions?
0:19:19.175 --> 0:19:29.255
Gabriel Bien-Willner
There's a there's a wide variety of practitioners out there and it may not be appropriate to set policy that allows everybody to do what they want.
0:19:29.265 --> 0:19:32.825
Gabriel Bien-Willner
When what they wanna do isn't itself grounded in evidence.
0:19:32.835 --> 0:19:33.565
Gabriel Bien-Willner
So that's one issue.
0:19:34.705 --> 0:19:36.135
Gabriel Bien-Willner
The other issue is how?
0:19:36.185 --> 0:19:36.735
Gabriel Bien-Willner
What is he?
0:19:36.745 --> 0:19:37.275
Gabriel Bien-Willner
Accepted.
0:19:37.285 --> 0:19:45.975
Gabriel Bien-Willner
Understood way to evaluate these patients and your engagement with these patients as best evidence suggests you do.
0:19:46.865 --> 0:20:6.5
Gabriel Bien-Willner
And then for the kind of Services we're ultimately going to be talking about, what is the value performing those additional services above the information that already exists above the practice decisions you would already render and how would it change those decisions in such a way that would be demonstrated to improve outcomes?
0:20:6.175 --> 0:20:8.715
Gabriel Bien-Willner
So I hope that helps to some degree.
0:20:8.725 --> 0:20:16.425
Gabriel Bien-Willner
We're this this entire thing is being constructed to get that information from you guys because if we don't, we're we don't want to make a bad decision.
0:20:16.435 --> 0:20:22.905
Gabriel Bien-Willner
We don't want to assume that we understand how these patients should be managed and treated and how these decisions should be made.
0:20:23.395 --> 0:20:24.435
Gabriel Bien-Willner
We'd rather hear from you.
0:20:28.295 --> 0:20:28.665
Gabriel Bien-Willner
OK.
0:20:28.675 --> 0:20:35.825
Gabriel Bien-Willner
And while that first question was pretty obvious and it wasn't anything we didn't already know, we just wanted to hear it from you to really confirm.
0:20:37.415 --> 0:20:37.765
Gabriel Bien-Willner
What?
0:20:37.825 --> 0:20:40.105
Gabriel Bien-Willner
What we had seen and how we were approaching this.
0:20:41.5 --> 0:20:43.575
Gabriel Bien-Willner
I'm gonna move on to the second question, if that's OK.
0:20:44.585 --> 0:20:53.145
Gabriel Bien-Willner
Do you accept that some low-risk Medicare patients should be treated with breast conserving surgery alone with DCIS?
0:20:54.345 --> 0:21:5.935
Gabriel Bien-Willner
Uh, and if so, how would you identify that population and specifically what variables at clinical information is relevant in for rendering that decision?
0:21:10.745 --> 0:21:18.55
Kimberly Van Zee
I think one very important variable that's not included in any biomarker or nomogram is the patient's life expectancy.
0:21:18.325 --> 0:21:21.965
Kimberly Van Zee
If the life expectancy is very short, we wanna be minimal.
0:21:22.915 --> 0:21:31.5
Kimberly Van Zee
But if you can be 65 these days and have a 30-year life expectancy with all of them running marathons, et cetera.
0:21:31.315 --> 0:21:35.425
Kimberly Van Zee
So we wanna have the right fit for the right patient.
0:21:35.715 --> 0:21:48.945
Kimberly Van Zee
So I think it's that balanced with their risk and balance with their risk tolerance and the and we know from four different randomized studies, radiation reduces the risk of recurrence by half and reduce the risk of invasive recurrence by half.
0:21:49.665 --> 0:21:56.775
Kimberly Van Zee
And so balancing that all out and you know, come up with what the right fit is for an individual patient.
0:21:56.785 --> 0:21:59.635
Kimberly Van Zee
And in my practice I do it with very much shared decision making.
0:22:0.85 --> 0:22:2.35
Kimberly Van Zee
One other thing is radiation has harm.
0:22:2.445 --> 0:22:7.15
Kimberly Van Zee
It has changes to the fibrosis to the texture of the breast, fibrosis and stuff like that.
0:22:7.25 --> 0:22:7.775
Kimberly Van Zee
Pretty minor.
0:22:8.45 --> 0:22:16.455
Kimberly Van Zee
It has expense harm, you know, financial toxicity, and rarely, rarely it can cause angiosarcoma or other types of sarcomas.
0:22:16.465 --> 0:22:20.495
Kimberly Van Zee
So it isn't to be taken lightly, even though it's, you know, very safe and proven for decades.
0:22:21.55 --> 0:22:32.195
Kimberly Van Zee
So I think you know there's definite pro and con of the two and there's definitely people over 65 that I think when the risks and benefits are weighed, should not get radiation.
0:22:33.455 --> 0:22:37.925
Alastair Thompson
So that shared decision making really underpins a loss of what we all do.
0:22:37.935 --> 0:23:6.525
Alastair Thompson
I said suspect and it's that risks and benefits and at the moment the clinical things we can use like grade like commute crisis are really pretty poor in terms of guiding us as to who might benefit from radiotherapy, which as you say can believe Dr. Van Zee radiotherapy has no safe lower dosage if you believe that the data from Sarah Darby the Oxford Overview Group and New England General Medicine.
0:23:6.535 --> 0:23:31.15
Alastair Thompson
So if we're going to give somebody radiation treatment to prevent her getting local in breast recurrence or developing invasive disease, we've gotta have some way of working out the benefit for that patient versus there will be no benefit and certainly using clinical parameters, assuming somebody is going to live more than three, five years into the future as most older women will.
0:23:31.345 --> 0:23:47.345
Alastair Thompson
Then we don't have a good diagnostic until we had recently they the ability to look at some genes and clinical markers in the decision RT test and other tests have failed to demonstrate a real benefit.
0:23:47.355 --> 0:23:52.185
Alastair Thompson
Oncotype particularly has failed to be beneficial and not established in clinical practice.
0:23:52.195 --> 0:24:2.155
Alastair Thompson
So I think we've been looking for something given that our clinical diagnostic skills, no matter how brilliant we may think we are at it, have not really yielded for our patients.
0:24:3.445 --> 0:24:14.955
Kimberly Van Zee
That, and I would argue that if you put together many of the different clinical and pathological and treatment variables, you actually are pretty good at predicting risk of or estimating risk of recurrence.
0:24:15.705 --> 0:24:16.115
Kimberly Van Zee
Umm.
0:24:16.845 --> 0:24:17.835
Kimberly Van Zee
As shown in.
0:24:17.425 --> 0:24:17.585
Eileen P. Connolly
But.
0:24:19.725 --> 0:24:24.35
Eileen P. Connolly
You can predict risk of recurrence, but I don't think you could predict benefit of radiation.
0:24:19.965 --> 0:24:20.255
Kimberly Van Zee
Go ahead.
0:24:20.25 --> 0:24:20.245
Alastair Thompson
Yeah.
0:24:24.45 --> 0:24:40.345
Eileen P. Connolly
I think decision or it is the first Test that I actually saw that really tell sorts out the low, the people who are in low risk, who benefit from radiation versus don't seem to get any benefit from it because the hard part is a lot of people will say, I know I may have a low relative risk, but I still get a benefit.
0:24:35.285 --> 0:24:35.735
Kimberly Van Zee
Well.
0:24:40.355 --> 0:24:54.235
Eileen P. Connolly
So I'm gonna take radiation and if you can show them, or at least have data that says you may not benefit from it, then it's easier to, you know, for them to say, I don't want it because people feel like you're taking it away from them.
0:24:49.305 --> 0:24:49.465
Kimberly Van Zee
So.
0:24:54.245 --> 0:24:58.815
Eileen P. Connolly
When you say you're not gonna get radiation, at least in my population, which is minority majority minority.
0:24:55.865 --> 0:24:57.805
Kimberly Van Zee
Yeah, Yep.
0:24:59.415 --> 0:25:0.65
Kimberly Van Zee
Yeah.
0:25:0.155 --> 0:25:0.725
Kimberly Van Zee
Agree.
0:25:0.735 --> 0:25:14.305
Kimberly Van Zee
But I would argue that the decision RT or the Prelude RX data is actually very preliminary, and if you read the editorial regarding the Vicini paper, I mean really it has not been validated.
0:25:14.315 --> 0:25:15.775
Kimberly Van Zee
That paper does not validate.
0:25:15.785 --> 0:25:26.475
Kimberly Van Zee
They came up with a new score in that paper and their prior cut points were not validated and so I don't think you can actually stay.
0:25:26.485 --> 0:25:48.315
Kimberly Van Zee
I mean, they say that they show a difference, but there's not statistically significant proof, and there's a very poor power in their low risk group because if you take someone who has a risk profile of 5% risk of recurrence at 10 years and you cut the risk in half by radiation, you need a huge number to prove that 2 1/2% benefit.
0:25:48.445 --> 0:25:56.275
Kimberly Van Zee
So I think the relative risk is still 50% like all the randomized trials show and what they're seizing on is low power in their Study.
0:25:56.365 --> 0:25:58.435
Kimberly Van Zee
So they didn't reach statistical significance.
0:26:0.35 --> 0:26:7.995
Alastair Thompson
Yeah, we need to be a bit wary about the opinions in editorials because they're not always, uh, entirely edit for that space as you suggest.
0:26:8.225 --> 0:26:15.605
Alastair Thompson
But if you take the evidence that's out there in the peer reviewed literature, I think it's pretty clear that you and I would agree.
0:26:15.615 --> 0:26:23.645
Alastair Thompson
Dr. Van Zee that the clinical factors alone are just not gonna do it in terms of choosing who gets radiotherapy with the potential risks and benefits.
0:26:23.655 --> 0:26:25.725
Alastair Thompson
And so, sure, there's others on this call.
0:26:25.735 --> 0:26:27.565
Alastair Thompson
I'll stop monopolizing things.
0:26:27.815 --> 0:26:32.545
Alastair Thompson
Who can cite some of the multiple studies that have suggested?
0:26:32.615 --> 0:26:41.495
Alastair Thompson
Actually there is a test now out there, and it's not Oncotype that that can help guide us in that shared decision making that you and I certainly agree on.
0:26:44.15 --> 0:26:45.645
Atif Khan
I don't know if we're jumping ahead.
0:26:45.695 --> 0:26:46.335
Atif Khan
Oh sorry, go ahead.
0:26:48.455 --> 0:26:49.835
Atif Khan
You're muted Dr. Williams.
0:26:48.855 --> 0:26:55.165
Gabriel Bien-Willner
We are definitely jumping ahead, but I do want it where we have a conversation.
0:26:49.365 --> 0:26:49.855
Kimberly Van Zee
You're muted.
0:26:49.565 --> 0:26:50.75
Eileen P. Connolly
You're muted.
0:26:55.175 --> 0:27:3.715
Gabriel Bien-Willner
I think you're you've already zoned zoomed in to some very contentious issues that I think are what the reason that this panel has been.
0:27:1.35 --> 0:27:1.375
Alastair Thompson
Umm.
0:27:4.365 --> 0:27:10.585
Gabriel Bien-Willner
Can I convened I if I could quickly touch on something?
0:27:10.595 --> 0:27:15.965
Gabriel Bien-Willner
Dr. Connolly said really quick, which I think I really to want to understand her perspective.
0:27:15.975 --> 0:27:20.175
Gabriel Bien-Willner
I is your sense of the ultimate.
0:27:21.255 --> 0:27:23.225
Gabriel Bien-Willner
And again, we're gonna go back and hit this again.
0:27:23.235 --> 0:27:24.695
Gabriel Bien-Willner
I apologize also for jumping ahead.
0:27:26.735 --> 0:27:54.5
Gabriel Bien-Willner
The fact that, is perceived that these tests we can differentiate, not necessarily a difference in risk for recurrence or IB TR or invasive cancer, but really whether the patient will yield some benefit to radiation that itself uh is the value to you is that is that correct or one of the major issues about.
0:27:51.175 --> 0:27:51.625
Eileen P. Connolly
Yes.
0:27:52.55 --> 0:27:53.35
Eileen P. Connolly
Yeah, I think that's.
0:27:54.15 --> 0:27:56.65
Eileen P. Connolly
Yeah, that's absolutely it.
0:27:56.75 --> 0:27:58.865
Eileen P. Connolly
It's the promise of it that you know the data and I agree.
0:27:58.875 --> 0:28:2.605
Eileen P. Connolly
I mean, prospective randomized data is going to happen.
0:28:2.615 --> 0:28:9.205
Eileen P. Connolly
Energy is proposing, and I think his moved forward, a randomized trial that's going to ask that specific question.
0:28:9.215 --> 0:28:25.975
Eileen P Connolly
Looking in the low-risk population, but given the evidence that we have, it's compelling at this point that it's hard not to want to use this as an additional tool for patients who you know, I've had women who I would say you don't need radiation, but they really insist that they wanted.
0:28:26.245 --> 0:28:35.435
Eileen P. Connolly
Then it helps to have something that's gonna sort those patients out and it's the same in the opposite direction, so yeah.
0:28:31.385 --> 0:28:31.625
Gabriel Bien-Willner
Let's see.
0:28:32.315 --> 0:28:32.655
Gabriel Bien-Willner
So let.
0:28:34.555 --> 0:28:38.405
Gabriel Bien-Willner
So let me let me then follow that up with two questions.
0:28:38.415 --> 0:28:53.635
Gabriel Bien-Willner
One is if it turned out that this test actually cannot differentiate patients who uh, don't benefit from radiation, and that's, would that change your mind on the value?
0:28:53.925 --> 0:29:11.475
Gabriel Bien-Willner
And it seems like you're also saying that it it also helps you have some sort of ammunition to put something in front of a patient to say, hey, you know, here's some evidence for why you should do this rather than some soft kinds of you know, we don't really know.
0:29:12.85 --> 0:29:16.55
Gabriel Bien-Willner
But you could say look, this says X and this makes helps us make a decision.
0:29:16.665 --> 0:29:21.285
Gabriel Bien-Willner
Even though you could have probably arrived at that conclusion without it, but it's OK.
0:29:22.205 --> 0:29:26.395
Eileen P. Connolly
No, I mean the clinical data is important because it helps you risks.
0:29:27.5 --> 0:29:34.595
Eileen P. Connolly
I'll let others speak, but it helps you risk stratify risk, sort patients, but it doesn't tell you it doesn't predict who's gonna benefit.
0:29:35.65 --> 0:29:41.835
Eileen P. Connolly
Every randomized trial that is, so far everyone, even if you're classified as low risk, you still had a benefit or tug.
0:29:41.845 --> 0:29:43.505
Eileen P. Connolly
9804 showed a benefit.
0:29:43.645 --> 0:29:44.595
Eileen P. Connolly
Those were supposed to be.
0:29:44.605 --> 0:29:48.655
Eileen P. Connolly
That's the ideal group of low-risk wide margins.
0:29:48.735 --> 0:30:0.595
Eileen P. Connolly
Majority took tamoxifen and there was still a benefit of radiation this in their data that's been you know they've validated and repeated cohorts pulls out a group that doesn't benefit.
0:30:0.845 --> 0:30:5.595
Eileen P. Connolly
I mean, I know doctor Van Zee Renzi is shaking her head.
0:30:4.975 --> 0:30:8.305
Kimberly Van Zee
No, I mean we need, we need a statistician.
0:30:8.315 --> 0:30:17.905
Kimberly Van Zee
I mean, I have some background in statistics, so maybe I'm more aware of some of these weaknesses in this data, but it did not show in the prespecified, the prelude.
0:30:8.855 --> 0:30:9.15
Eileen P. Connolly
Yeah.
0:30:17.915 --> 0:30:28.605
Kimberly Van Zee
RT did not show in the prespecified cut offs, prediction or prognosis in their proposed validity trial with the randomized data from Swedish, even though they say they did.
0:30:28.615 --> 0:30:29.325
Kimberly Van Zee
They didn't.
0:30:29.395 --> 0:30:32.655
Kimberly Van Zee
If you look at the confidence intervals, there was no statistically significant difference.
0:30:34.425 --> 0:30:38.75
Kimberly Van Zee
And again it's, it's actually articulated very clearly.
0:30:38.85 --> 0:30:40.155
Kimberly Van Zee
I mean, this is not opinion, this is data.
0:30:40.165 --> 0:30:42.795
Kimberly Van Zee
It was an analysis done by this editorial.
0:30:42.985 --> 0:30:47.175
Kimberly Van Zee
Doctor Woodward, I don't know her, but she very clearly pointed it out.
0:30:47.185 --> 0:30:54.575
Kimberly Van Zee
And is very articulate about it and also I just big picture and I don't know if you know this Dr. Bien-Willner.
0:30:54.585 --> 0:31:3.275
Kimberly Van Zee
But both Oncotype DCIS score and Prelude have incorporated clinical pathologic variables into their score.
0:31:3.285 --> 0:31:11.145
Kimberly Van Zee
So when you get their score for DCIS score, you get age, size and the time period of surgery is rolled in there that they don't really tell you.
0:31:11.315 --> 0:31:16.185
Kimberly Van Zee
And for Prelude from the beginning, they have age, size, margin status and palpability.
0:31:16.715 --> 0:31:25.205
Kimberly Van Zee
And what they don't tell you is what proportion of their prediction is from those clinical pathologic variables as compared to the biological signature.
0:31:25.915 --> 0:31:40.295
Kimberly Van Zee
Dr. Khan and I were in a meeting where actually the Prelude RT scientific folks told us to our face that minor monogram works better than their signature, but they never published that.
0:31:42.465 --> 0:31:43.905
Alastair Thompson
So a couple of things.
0:31:43.915 --> 0:31:51.335
Alastair Thompson
First of all I do know Doctor Woodward and she's a friend, so I'm not gonna knock her here, but she's not a statistician.
0:31:51.405 --> 0:32:4.115
Alastair Thompson
And as you correctly pointed out, as statistics should really be left of the statisticians, the second thing to say is that I'm not going to base anything on a single study.
0:32:4.125 --> 0:32:33.435
Alastair Thompson
And when you have a host of publications in prestigious journals like clinical Cancer Research, which have been peer reviewed, which have been through degree of scrutiny that I think is pretty formidable when you have multiple publications all coming up with a similar gist that attest that can tell you will or you will not benefit from radiotherapy is actually going to be clinically useful to us into the future.
0:32:27.415 --> 0:32:27.535
Kimberly Van Zee
But.
0:32:34.315 --> 0:32:43.465
Kimberly Van Zee
But the clinical Cancer Research paper was the population they were testing added in it it in was their development population.
0:32:43.475 --> 0:32:55.365
Kimberly Van Zee
It was not an independent population, and if you read that analysis carefully, actually in one of the analysis, the year of Surgery was more predictive then was there Prelude, RT, test.
0:32:45.65 --> 0:32:45.215
Alastair Thompson
Yeah.
0:32:56.285 --> 0:32:59.975
Kimberly Van Zee
But then they turn change things around and included year and excluded people.
0:32:59.985 --> 0:33:3.795
Kimberly Van Zee
I mean, they just, you know, massage the data a bit.
0:33:1.975 --> 0:33:5.565
Alastair Thompson
I I'm not basing and playing on a single publication.
0:33:4.715 --> 0:33:8.965
Kimberly Van Zee
Uh, no, I know, but all of them have issues like that.
0:33:5.715 --> 0:33:8.175
Alastair Thompson
What I would say is that, yeah.
0:33:8.975 --> 0:33:9.765
Kimberly Van Zee
That's what I'm saying.
0:33:9.775 --> 0:33:12.5
Kimberly Van Zee
Each one there, and the most recent one.
0:33:12.15 --> 0:33:13.435
Kimberly Van Zee
They added this RRT.
0:33:13.445 --> 0:33:28.15
Kimberly Van Zee
They're residual risk score, but it's not they, and they don't tell you how they developed it and in what population they developed it and they kind of threw it in there and they changed the cut points for the original one and added an A third one.
0:33:15.555 --> 0:33:15.765
Alastair Thompson
Umm.
0:33:16.425 --> 0:33:16.695
Eileen P. Connolly
Right.
0:33:28.305 --> 0:33:30.535
Kimberly Van Zee
And it's very sketchy whenever you see that.
0:33:30.545 --> 0:33:38.935
Kimberly Van Zee
As a statistician, you wonder what's going on because the components of the RT are the same components as in the original DCIS.
0:33:33.785 --> 0:33:34.995
Alastair Thompson
Well, you, you.
0:33:39.265 --> 0:33:42.615
Kimberly Van Zee
Whatever decision NRT score, so what did they do?
0:33:41.885 --> 0:33:42.15
Alastair Thompson
Yeah.
0:33:43.415 --> 0:33:45.625
Eileen P. Connolly
No, I think it's a separate added test.
0:33:44.145 --> 0:33:44.315
Atif Khan
But.
0:33:45.635 --> 0:33:47.935
Eileen P. Connolly
I mean that's my understanding when they, yeah.
0:33:46.65 --> 0:33:46.505
Kimberly Van Zee
Yeah, but.
0:33:47.445 --> 0:33:51.635
Kimberly Van Zee
But in their paper, it says it's the same components saying.
0:33:50.695 --> 0:33:51.125
Atif Khan
If I may.
0:33:52.345 --> 0:33:52.675
Eileen P. Connolly
App.
0:33:54.155 --> 0:33:56.565
Kimberly Van Zee
Configure differently but same component, say.
0:33:57.655 --> 0:34:17.245
John Williams
I'm going to just share a larger viewpoint on this in making decisions about patients with DCS, which is complicated, it's incredibly complicated if you need chemotherapy for invasive cancer, it's pretty clear in most situations, DCS, we're tailoring a process, but for many years, we're using all the gross data.
0:34:17.295 --> 0:34:21.945
John Williams
It's kind of like a drone flying over a car and distress that stopped on the side of the road.
0:34:22.255 --> 0:34:26.575
John Williams
People outside looking around you can tell that maybe there's a margin of people around it.
0:34:26.615 --> 0:34:31.455
John Williams
Margins for DCIS, you can tell maybe a grade these sorts of things we've been using for decades.
0:34:32.965 --> 0:34:35.455
John Williams
But this test really helps U.S.
0:34:35.505 --> 0:34:36.375
John Williams
Open the hood.
0:34:36.385 --> 0:34:43.535
John Williams
Look at the engine and get to a better answer to Taylor what's needed for the car to work now.
0:34:43.545 --> 0:35:10.485
John Williams
Certainly our researches, their critics and then their supporters and we can have this debate, these are debates at conferences, but I would also share with you that our goal going back to the question before last was to find people that we do not do radiation that otherwise will get radiation when you have the drone flight over the 36,000 feet in the sky.
0:35:10.695 --> 0:35:15.5
John Williams
And I'm not a statistician and we can argue that forever here.
0:35:15.175 --> 0:35:17.165
John Williams
But this test has proven its worth.
0:35:17.175 --> 0:35:36.5
John Williams
Clinically, it is intended and also as being utilized and nomograms are seldom being utilized, but also because it has proven to us that it's out of clinical utility making decisions one on one with women who are all individualized and giving them the best information that's available.
0:35:17.885 --> 0:35:19.725
Kimberly Van Zee
It hasn't, no.
0:35:36.15 --> 0:35:37.65
John Williams
So I just wanted to share that.
0:35:37.915 --> 0:35:38.885
Kimberly Van Zee
But you can use.
0:35:38.895 --> 0:35:42.885
Kimberly Van Zee
You can make something or perceive that something has clinical utility.
0:35:42.895 --> 0:35:56.425
Kimberly Van Zee
When you make a decision based on incorrect information and you're making incorrect choices and you still measure it as clinical utility in that study, they didn't note that many of the people fit the RTOG criteria, which was randomized study.
0:35:56.695 --> 0:36:3.845
Kimberly Van Zee
And despite that, they went with they were telling him to do radiation until they looked at the decision RT Test.
0:36:4.315 --> 0:36:16.565
Kimberly Van Zee
But big, big picture stepping back right now, there is no evidence that any of these biosignatures is any better than a combination of clinical pathologic factors like the nomogram.
0:36:16.85 --> 0:36:17.5
Alastair Thompson
That's nonsense.
0:36:16.615 --> 0:36:17.575
Kimberly Van Zee
There is no data.
0:36:17.415 --> 0:36:21.895
Alastair Thompson
After nonsense that is complete nonsense that is just completely out.
0:36:18.515 --> 0:36:22.965
John Williams
And separate, you can't pay back at work was gone.
0:36:19.655 --> 0:36:20.605
Kimberly Van Zee
Yeah, hold on.
0:36:20.755 --> 0:36:22.165
Kimberly Van Zee
No, no show.
0:36:22.335 --> 0:36:24.395
Alastair Thompson
I'm sorry you can't just make that statement.
0:36:22.545 --> 0:36:22.955
Kimberly Van Zee
Hold on.
0:36:23.985 --> 0:36:27.235
Kimberly Van Zee
Well, well, I I'm happy to hear.
0:36:24.405 --> 0:36:25.735
Alastair Thompson
I think you can get away with it and.
0:36:26.195 --> 0:36:27.335
John Williams
Almost inflammatory.
0:36:27.245 --> 0:36:29.815
Kimberly Van Zee
I'm happy to hear a head-to-head comparison.
0:36:30.155 --> 0:36:47.125
Kimberly Van Zee
There are no published area under the RFC curves or calibration curves for the biosignature alone on either of them, there is no incorporation of the use of tamoxifen or endocrine therapy, which has been proven to reduce the risk of recurrence by half, and none of them incorporate that.
0:36:47.135 --> 0:36:51.775
Kimberly Van Zee
So by definition, they're inaccurate in that if they're doing.
0:36:50.515 --> 0:36:53.405
Alastair Thompson
Now they're looking at radiation and not looking at tamoxifen treatment.
0:36:53.415 --> 0:37:1.695
Alastair Thompson
And there are some countries around the world who never use tamoxifen because it is not effective in terms of survival for patients with breast cancer.
0:36:53.685 --> 0:36:54.165
Kimberly Van Zee
Right. But.
0:37:0.705 --> 0:37:1.975
Kimberly Van Zee
Well, neither is radiation.
0:37:1.705 --> 0:37:2.365
Alastair Thompson
Doesn't even.
0:37:2.245 --> 0:37:2.775
Kimberly Van Zee
Neither is.
0:37:2.715 --> 0:37:3.685
Alastair Thompson
Well, exactly.
0:37:2.865 --> 0:37:3.685
Kimberly Van Zee
Neither is radiation.
0:37:3.695 --> 0:37:4.5
Alastair Thompson
It's not.
0:37:4.15 --> 0:37:12.585
Alastair Thompson
Radiotherapy is not effective at its survival improvement then we should be defining those patients who do not need radiotherapy because it won't benefit from them.
0:37:12.935 --> 0:37:19.25
Alastair Thompson
It won't benefit them, and we should be defining those patients who might get benefit from radiotherapy and therefore should be given it.
0:37:13.275 --> 0:37:13.395
Kimberly Van Zee
But.
0:37:19.35 --> 0:37:29.935
Alastair Thompson
That's the whole point of having some prognostic diagnostic tool, which is why we're convening today and not just using hearsay and algorithms that you know are not widely adopted.
0:37:28.405 --> 0:37:29.645
Kimberly Van Zee
I'm not using here.
0:37:30.135 --> 0:37:34.565
Kimberly Van Zee
That's what I'm concerned about is the way the data are presented.
0:37:34.575 --> 0:37:35.385
Kimberly Van Zee
It's misleading.
0:37:35.395 --> 0:37:39.475
Kimberly Van Zee
A lot of this data is misleading, but back to enter back.
0:37:37.315 --> 0:37:42.135
Alastair Thompson
In peer reviewed publications and multiple journals it they can't all be around.
0:37:38.285 --> 0:37:38.665
Atif Khan
Alright.
0:37:39.395 --> 0:37:39.775
Atif Khan
That's.
0:37:41.295 --> 0:37:44.435
Kimberly Van Zee
Back to endocrine therapy.
0:37:43.275 --> 0:37:44.805
John Williams
But Dr. Khan wants you.
0:37:44.825 --> 0:37:48.535
Atif Khan
Yeah, I sure it.
0:37:44.935 --> 0:37:48.955
John Williams
Let Dr. Khan uh, give us a different perspective.
0:37:49.25 --> 0:37:49.315
Atif Khan
Yeah.
0:37:49.325 --> 0:37:51.255
Atif Khan
If I may, if I may just take one step back.
0:37:52.45 --> 0:37:52.885
Atif Khan
Just to go back to.
0:37:55.915 --> 0:38:0.445
Atif Khan
The original question that was posed, which is women who can forgo radiation?
0:38:0.455 --> 0:38:3.985
Atif Khan
I think the answer everyone's answer is yes, there are women who can forgo radiation.
0:38:4.895 --> 0:38:13.605
Atif Khan
The approach that we've taken at MSK is and it's not perfect, but it's sort of the approach that we're running currently is we ask the opposite question.
0:38:13.615 --> 0:38:35.695
Atif Khan
Who do we believe absolutely needs radiation and we've sort of identified 4 features that we as a consensus of experts believe is an automatic indication for radiation and they are number one, grade 3 like high grade disease #2 size over 2.5 centimeters #3A close margin which we've defined as less than two millimeters.
0:38:36.765 --> 0:38:45.75
Atif Khan
Uh, meaning an unremediated close margin, meaning that the patient is not willing to go back for reexcision or the recession is not planned.
0:38:45.245 --> 0:38:47.215
Atif Khan
And then age less than 4D.
0:38:47.225 --> 0:39:1.385
Atif Khan
And so if in the presence of even one of these risk factors, we would consider radiotherapy and in the absence of all four of these risk factors, which by the way is a huge number of patients, there is a huge number of patients that don't have any of these four things.
0:39:2.55 --> 0:39:7.145
Atif Khan
We sort of defer the decision on we don't consider radiation to be indicated to.
0:39:7.155 --> 0:39:10.565
Atif Khan
However, we don't consider radiation to be wrong.
0:39:10.575 --> 0:39:17.65
Atif Khan
We think it would be OK for any woman with DCIS to receive radiation in this bulk of women who don't fit these criteria.
0:39:17.75 --> 0:39:30.675
Atif Khan
We would say, you know, going back to this idea of shared decision making, all this is to say that our current state of how we are sort of deciding and adjudicating treatment for DCIS is, is very flawed.
0:39:31.105 --> 0:39:38.165
Atif Khan
There's a tremendous, you know, room for improvement here and I think I don't think anybody would disagree with that.
0:39:38.265 --> 0:39:40.185
Atif Khan
Like we could be doing this better, right?
0:39:41.185 --> 0:39:48.215
Atif Khan
Umm, now coming to the signatures, I think the signatures are a natural extension of what's happening all across oncology.
0:39:48.225 --> 0:39:56.195
Atif Khan
So I think to use biology signatures to try to adjudicate and risk stratify DCIS patients is a perfectly rational strategy.
0:39:56.425 --> 0:39:57.25
Atif Khan
We can get it.
0:39:57.35 --> 0:40:2.695
Atif Khan
I can speak to, and we get the data in one second, but before even that, the thing I'd like to really point I think is really important.
0:40:3.965 --> 0:40:9.635
Atif Khan
If we had a perfect assay, like if we had the assay that was sent down on a mountain from God, he was absolutely the perfect assay.
0:40:9.705 --> 0:40:14.715
Atif Khan
Analytically, you know clinically the prediction was there.
0:40:14.725 --> 0:40:15.495
Atif Khan
The prognosis?
0:40:15.645 --> 0:40:21.495
Atif Khan
It was just the perfect assay, and it was handed to me, and I was gonna be the person that was going to bring this to the world.
0:40:21.725 --> 0:40:28.495
Atif Khan
It would still be very hard because to find the data sets to convincingly show people guys, this actually really works.
0:40:28.505 --> 0:40:32.135
Atif Khan
That's really complicated because people will say, well, that data is old.
0:40:32.265 --> 0:40:35.145
Atif Khan
You know, those patients were not treated the way that we treat patients now.
0:40:36.75 --> 0:40:42.485
Atif Khan
There's all types of problems that one would encounter, even as one was trying to validate the perfect assay.
0:40:42.815 --> 0:40:52.575
Atif Khan
Just that's just the nature of the business and that's sort of why you're seeing the disagreements that you're seeing here umm, now coming to the, you know, well, do you?
0:40:53.215 --> 0:40:54.645
Atif Khan
I think here's what we can say.
0:40:54.655 --> 0:41:4.205
Atif Khan
I think quite with the high degree of confidence, I think that the Prelude DX assay reclassifies patients based on from their clinical path.
0:41:4.215 --> 0:41:14.995
Atif Khan
I think that that's true, meaning that if you stratify patients by Clint Path and then run their assay, it's not, there's a huge amount of resorting that's happening by the asset.
0:41:15.5 --> 0:41:16.55
Atif Khan
So I think that's true.
0:41:17.45 --> 0:41:25.315
Atif Khan
Uh, meaning that it's adding some information that's not simply just, you know, the Clin path and we can I didn't prepare any slides or anything.
0:41:25.325 --> 0:41:30.365
Atif Khan
But if you look at the data, it's very clear that there are women are being the tumors are being reclassified.
0:41:30.965 --> 0:41:48.735
Atif Khan
I think the final bit of that is ok what is the prognostic or predictive implication of this resorting that's happening by the assay, and you know, I think I think there are initial tests that we're running, you know more limited data sets were very encouraging.
0:41:48.745 --> 0:41:50.405
Atif Khan
I would say I think it was.
0:41:51.525 --> 0:41:52.335
Atif Khan
I was quite excited.
0:41:52.345 --> 0:41:58.395
Atif Khan
I thought they were actually on to something when they went to validate it and the randomized data set.
0:41:58.845 --> 0:41:59.875
Atif Khan
I think Kim is right.
0:41:59.885 --> 0:42:3.795
Atif Khan
It did not hold up to the same level like it didn't really.
0:42:4.185 --> 0:42:8.445
Atif Khan
It didn't hold up as an independent interactor.
0:42:8.455 --> 0:42:10.445
Atif Khan
You know, in that analysis, I think that that is true.
0:42:11.325 --> 0:42:15.75
Atif Khan
Umm, I think what they did subsequently was that they added to the model.
0:42:15.85 --> 0:42:17.235
Atif Khan
They added three additional markers, right.
0:42:17.245 --> 0:42:18.245
Atif Khan
They had was.
0:42:19.75 --> 0:42:22.125
Atif Khan
Umm, they added three additional I've.
0:42:22.495 --> 0:42:26.825
Kimberly Van Zee
They're the same ones that are in the original biosignature they say in their paper.
0:42:27.875 --> 0:42:28.535
Atif Khan
No, Kim, that's.
0:42:28.5 --> 0:42:31.115
Kimberly Van Zee
It's the pathway that OK, the K rouse.
0:42:30.265 --> 0:42:30.585
Atif Khan
Right.
0:42:30.595 --> 0:42:40.35
Atif Khan
The keras is not in there, so the originals are her two key 67, Cox 2, Saya box 81P16 and the residual risk assay.
0:42:32.585 --> 0:42:33.475
Kimberly Van Zee
Yep, yeah it.
0:42:37.55 --> 0:42:39.25
Kimberly Van Zee
Yeah, I'll read it.
0:42:40.45 --> 0:42:42.455
Atif Khan
There's go ahead.
0:42:41.205 --> 0:42:51.675
Kimberly Van Zee
I'll read it and thus an algorithm was prespecified to combine biomarkers parenthesis used by the DSS biosignature in a novel manner.
0:42:52.885 --> 0:42:59.895
Kimberly Van Zee
So they use the same biomarkers to make this RT, and it's in the EGFR.
0:42:59.905 --> 0:43:1.795
Kimberly Van Zee
Her 2K Ras pathway.
0:43:2.5 --> 0:43:9.755
Kimberly Van Zee
But it's the same biomarkers, they just reconfigured them and this is in Vicini that's vaccine.
0:43:6.15 --> 0:43:17.125
Atif Khan
I think that, yeah, I think the source data, yeah, the source data from which they pulled the original biomarkers is the same source data from which they pulled it or right.
0:43:6.675 --> 0:43:7.85
Eileen P. Connolly
I think they.
0:43:14.65 --> 0:43:18.615
Alastair Thompson
Yeah, there's no additional markets, that it in that the.
0:43:16.145 --> 0:43:18.525
Kimberly Van Zee
No, it's the same markers stain markers.
0:43:17.455 --> 0:43:41.745
Atif Khan
Alright, but they may have been weighted differently or you know, but essentially the Analytics of the assay was tuned, you know for the you know for that second and that second coming of the test in which there's three categories, the low risk, elevated risk and residual risk and you know I think in that in that paper the latest paper with the residual risk, I do find it compelling.
0:43:21.225 --> 0:43:21.515
Kimberly Van Zee
Right.
0:43:28.135 --> 0:43:28.315
Kimberly Van Zee
But.
0:43:31.655 --> 0:43:31.975
Eileen P. Connolly
Right.
0:43:41.755 --> 0:43:52.865
Atif Khan
I think you know it's sort of the best thing that we have, especially when you compare it to the Oncotype assay, which is really like their development is so behind.
0:43:46.85 --> 0:43:46.245
Alastair Thompson
Umm.
0:43:52.875 --> 0:43:54.5
Atif Khan
It's really just prognostic.
0:43:54.15 --> 0:43:59.155
Atif Khan
I haven't really seen kind of a demonstration of that assay being predictive of radiotherapy benefit.
0:43:58.305 --> 0:43:59.735
Alastair Thompson
You think we've given up on it?
0:43:59.275 --> 0:43:59.965
Kimberly Van Zee
So why don't?
0:43:59.635 --> 0:44:0.65
Eileen P. Connolly
It's.
0:43:59.745 --> 0:44:0.185
Alastair Thompson
Uh, it's.
0:44:0.75 --> 0:44:1.395
Eileen P. Connolly
Yeah, it's not predictive at all.
0:44:0.195 --> 0:44:7.105
Alastair Thompson
I think they've given it completely as being unable to really progress with DCIS and then leave marketing it.
0:44:3.115 --> 0:44:3.355
Kimberly Van Zee
Well.
0:44:5.635 --> 0:44:15.855
Kimberly Van Zee
Why don't we take the Prelude, RT and compare it head-to-head with the nomogram, for example, which?
0:44:15.865 --> 0:44:27.55
Kimberly Van Zee
No, there's nothing so special about the nomogram, except it combines a lot of significant variables and a lot of even they weren't statistically significant, but they had made clinical sense and compare it head-to-head.
0:44:27.355 --> 0:44:32.555
Kimberly Van Zee
And we know the answer actually before the residual risk, the answer was the nomogram did better.
0:44:32.625 --> 0:44:34.205
Kimberly Van Zee
That's what the guy said.
0:44:34.215 --> 0:44:36.565
Kimberly Van Zee
The scientific officer told us that.
0:44:35.415 --> 0:44:36.65
Alastair Thompson
Yeah.
0:44:36.195 --> 0:44:36.545
Alastair Thompson
So.
0:44:36.555 --> 0:44:36.765
Alastair Thompson
So.
0:44:36.815 --> 0:44:43.985
Alastair Thompson
So that's, that's hearsay, Kimberly and I don't wish to be rude and forgive me for saying this, but you're the person that came up with the nomogram.
0:44:38.865 --> 0:44:41.165
Kimberly Van Zee
No, I'm saying he said that.
0:44:39.985 --> 0:44:40.295
Atif Khan
Ah.
0:44:43.995 --> 0:44:50.695
Alastair Thompson
So at Memorial and that may apply perfectly well to memorial patients who are very sub subset.
0:44:50.705 --> 0:44:55.205
Alastair Thompson
As I know from having been there 30 years ago, but that's not the real world.
0:44:55.215 --> 0:45:14.165
Alastair Thompson
What we're talking about here, I feel is trying to do something better for our patient populations who may be older patients who may benefit from radiotherapy or may not behave benefit from radiotherapy and whether it's tumor grade alone, whether it's the presence of Camino necrosis where it's almost a guess what the pathologists are going to say.
0:45:14.175 --> 0:45:19.265
Alastair Thompson
And I can forward the publications on that to the committee if they wish, the committee, if they wish.
0:45:19.395 --> 0:45:21.425
Alastair Thompson
But we need something that's better.
0:45:21.435 --> 0:45:24.105
Alastair Thompson
And Oncotype DCIS doesn't do it.
0:45:22.45 --> 0:45:22.755
Kimberly Van Zee
Agreed.
0:45:23.65 --> 0:45:25.115
Kimberley Van Zee
Agreed. Agreed.
0:45:24.235 --> 0:45:30.45
Alastair Thompson
The nomogram, even if it didn't, isn't accepted, isn't widely used, is just not something.
0:45:30.55 --> 0:45:32.795
Alastair Thompson
And I'm sorry to say this to this use out which will bring.
0:45:30.165 --> 0:45:31.196
Kimberly Van Zee
Because there's no E.
0:45:31.85 --> 0:45:42.595
John Williams
We we have to make clinical decisions in a situation where we have to tailor the information in a shared decision making fashion, so we've got nomograms.
0:45:39.475 --> 0:45:39.655
Alastair Thompson
Yeah.
0:45:40.435 --> 0:45:40.855
Kimberly Van Zee
Umm.
0:45:42.605 --> 0:45:53.125
John Williams
We've got other factors, but this signature has and regardless, I understand that Kim disagrees with really the four of us, and we welcome that.
0:45:53.135 --> 0:45:54.245
John Williams
That's why we're here.
0:45:54.125 --> 0:45:54.865
Alastair Thompson
Yeah, it's good.
0:45:54.775 --> 0:46:13.405
John Williams
But that is also why that let let me just finish, please for a second is that I understand, but you know, but we as clinicians need to make sophisticated decisions to decide, number one, which women do not require radiation.
0:45:55.895 --> 0:45:58.405
Kimberly Van Zee
I just want the data; I just want the evidence.
0:46:13.595 --> 0:46:16.925
John Williams
And this test is incredibly helpful in doing so.
0:46:17.35 --> 0:46:24.855
John Williams
And for those that we otherwise might avoid ration, we might not give radiation highly needed and have a great benefit from it.
0:46:24.935 --> 0:46:53.495
John Williams
So ultimately this decision one on one with patients shared decision making comes out different for you and you and you at the same clinical factors has to include all of this information and this is a leap forward in us making good decisions in a precision medicine fashion and without it we're still hovering over the car that's stalled and we're not knowing what to do or what to guide them except for the call the tow truck.
0:46:53.755 --> 0:46:57.125
John Williams
But when you look under the hood, maybe there's just a wire.
0:46:57.135 --> 0:46:59.85
John Williams
Disconnect you, reconnect it, move forward.
0:46:59.95 --> 0:47:0.155
John Williams
So I just want to share that.
0:46:59.795 --> 0:47:5.55
Kimberly Van Zee
But that's a wonderful goal, but I just want evidence that we've achieved that.
0:47:5.275 --> 0:47:8.165
Kimberly Van Zee
Why can't we have a head-to-head comparison?
0:47:8.655 --> 0:47:10.185
Kimberly Van Zee
We'll show me Doctor Thompson.
0:47:10.195 --> 0:47:11.105
Kimberly Van Zee
You said it existed.
0:47:11.115 --> 0:47:20.435
Kimberly Van Zee
I have never seen any head-to-head comparison of the nomogram with either Prelude RT or the Oncotype head-to-head it.
0:47:19.645 --> 0:47:25.595
Alastair Thompson
So that's that speaks volumes for the fact that two different companies just don't value the nomogram.
0:47:20.445 --> 0:47:21.225
Kimberly Van Zee
It doesn't exist.
0:47:25.605 --> 0:47:30.335
Alastair Thompson
Forgive me for saying it that way in in wanting to to validate across and.
0:47:26.165 --> 0:47:26.425
Kimberly Van Zee
Yep.
0:47:28.885 --> 0:47:29.295
Kimberly Van Zee
Right.
0:47:29.305 --> 0:47:33.285
Kimberly Van Zee
Because it would, because it would ruin their commercial profits and they would be.
0:47:33.295 --> 0:47:46.835
Kimberly Van Zee
It would be a useless test and if you can use a free test versus a $6400 test, why not do it with our taxpayer dollars and the $6400 test is gonna be worthless if someone actually compared it.
0:47:39.635 --> 0:47:39.795
Alastair Thompson
Yeah.
0:47:46.845 --> 0:47:51.515
Kimberly Van Zee
And that's why, even though they compared it, they never published it because it would ruin their business model.
0:47:52.185 --> 0:47:53.275
Alastair Thompson
Yeah, I I love.
0:47:52.415 --> 0:47:53.785
Kimberly Van Zee
And but I.
0:47:52.415 --> 0:47:54.775
Gabriel Bien-Willner
Umm anyways, I'm stepping here real.
0:47:52.505 --> 0:47:53.265
Atif Khan
Kim, I think.
0:47:53.325 --> 0:47:57.225
Alastair Thompson
I love to hear saying, but that's not what we're here to discuss well.
0:47:53.855 --> 0:47:54.65
Eileen P. Connolly
Don't.
0:47:55.365 --> 0:47:57.155
Atif Khan
Yeah, I think him.
0:47:56.515 --> 0:48:9.365
John Williams
Gabriel, you are so far beyond what we should be discussing, and we have so much more to discuss, and clinical things and I understand there's a Kim really has a a problem with data which I value.
0:47:56.755 --> 0:47:57.925
Gabriel Bien-Willner
I very much liked it.
0:47:57.935 --> 0:47:58.875
Gabriel Bien-Willner
Just step in here.
0:47:58.885 --> 0:48:0.55
Gabriel Bien-Willner
Uh, if possible.
0:48:6.75 --> 0:48:6.255
Alastair Thompson
Yeah.
0:48:9.635 --> 0:48:11.405
John Williams
But we have other information.
0:48:11.415 --> 0:48:15.745
John Williams
We can't hijack our whole discussion on on question #2.
0:48:13.55 --> 0:48:13.725
Gabriel Bien-Willner
Yes.
0:48:14.75 --> 0:48:15.315
Gabriel Bien-Willner
Thank you, Doctor Williams.
0:48:14.305 --> 0:48:14.445
Alastair Thompson
Yeah.
0:48:15.755 --> 0:48:20.985
John Williams
And so I I kind of would like to turn it back to you because we we really have a lot more to to share.
0:48:21.215 --> 0:48:25.925
John Williams
I mean or there's information that you want from all five of us and let's move forward with that.
0:48:25.935 --> 0:48:27.835
John Williams
I think we all understand that.
0:48:26.115 --> 0:48:26.755
Gabriel Bien-Willner
This this is.
0:48:29.15 --> 0:48:30.185
Gabriel Bien-Willner
This is been great.
0:48:29.195 --> 0:48:29.715
Alastair Thompson
Thank you, Joe.
0:48:30.295 --> 0:48:31.965
Gabriel Bien-Willner
Thank you so much and I appreciate that.
0:48:31.975 --> 0:48:44.525
Gabriel Bien-Willner
I do want to kind of circle back to to I do want answers to these other questions that are clinically based that hopefully get us to those variables that require review and consideration before I do.
0:48:44.535 --> 0:48:53.445
Gabriel Bien-Willner
So, I do want to ask Dr. Khan a quick question before we move on to as we are going to eventually played it back to this.
0:48:53.455 --> 0:48:58.545
Gabriel Bien-Willner
But you mentioned that there was some evidence that you found was compelling in your review.
0:48:58.795 --> 0:49:5.815
Gabriel Bien-Willner
Can you quickly summarize what specifically you found compelling, even though I, like I said this again?
0:49:7.165 --> 0:49:7.495
Atif Khan
Sure.
0:49:7.505 --> 0:49:10.295
Atif Khan
I think you know this has been alluded to earlier.
0:49:10.305 --> 0:49:25.215
Atif Khan
When you look at the hazard ratios in the different risk groups the assay is performing in a predictive way, meaning that the hazard ratios are are lower with radiation and the elevated and elevated with the residual risk group.
0:49:25.435 --> 0:49:28.875
Atif Khan
And that's not true for the low-risk group.
0:49:29.385 --> 0:49:32.625
Atif Khan
And you know that that's the first I think that.
0:49:34.955 --> 0:49:43.185
Atif Khan
That's something that did not exist before, and I think you know that, you know, there is interest in this, as Eileen was saying, the NRG is going to advance the concept.
0:49:43.195 --> 0:49:46.405
Atif Khan
So it's not like, you know, the community at large is ignoring this.
0:49:46.415 --> 0:49:54.45
Atif Khan
I think there is interest in improving the outcomes like our decisional matrix for these patients.
0:49:54.375 --> 0:50:0.225
Atif Khan
I think the idea that was alluded to earlier that this is another data point that can assist in shared decision making.
0:50:0.235 --> 0:50:2.165
Atif Khan
Like even today, I think that's also true.
0:50:3.125 --> 0:50:11.945
Atif Khan
Umm, I think the ultimate validation will happen in some prospective you know manner, but that's going to take years to, you know to sort of.
0:50:11.755 --> 0:50:14.145
Eileen P. Connolly
It's going to take a decade.
0:50:14.275 --> 0:50:15.45
Eileen P. Connolly
I mean, realistically.
0:50:14.395 --> 0:50:15.425
Atif Khan
Gather.
0:50:15.295 --> 0:50:15.555
Kimberly Van Zee
And.
0:50:15.875 --> 0:50:16.205
Atif Khan
Yeah.
0:50:16.215 --> 0:50:16.705
Atif Khan
And we can't.
0:50:16.605 --> 0:50:16.805
Atif Khan
Yeah.
0:50:16.685 --> 0:50:16.935
Gabriel Bien-Willner
Soon.
0:50:16.715 --> 0:50:18.55
Atif Khan
I don't think we, yeah.
0:50:18.215 --> 0:50:18.605
Gabriel Bien-Willner
OK.
0:50:18.305 --> 0:50:26.35
Kimberly Van Zee
And an independent data independent data set, though too we need an independent data set, not the set in which it was developed.
0:50:18.655 --> 0:50:19.45
Gabriel Bien-Willner
Thank you.
0:50:18.835 --> 0:50:18.975
Alastair Thompson
The.
0:50:19.55 --> 0:50:22.935
Gabriel Bien-Willner
I think you've.
0:50:26.355 --> 0:50:27.245
John Williams
Disagree this.
0:50:26.395 --> 0:50:26.785
Eileen P. Connolly
But the.
0:50:26.575 --> 0:50:28.525
Gabriel Bien-Willner
You've answered my question.
0:50:26.585 --> 0:50:28.495
Atif Khan
It's hard to forget that, though, like it's.
0:50:27.825 --> 0:50:28.75
John Williams
It's.
0:50:28.95 --> 0:50:28.285
John Williams
Good.
0:50:28.505 --> 0:50:29.505
Atif Khan
Yeah, it's hard to get that.
0:50:28.515 --> 0:50:28.605
John Williams
To.
0:50:28.635 --> 0:50:32.465
John Williams
Move forward, without a doubt the data is good enough and move forward.
0:50:28.775 --> 0:50:30.405
Gabriel Bien-Willner
Thank you, Dr. Kahn.
0:50:30.465 --> 0:50:31.585
Gabriel Bien-Willner
Thank you answered my question.
0:50:32.475 --> 0:50:35.805
John Williams
In my opinion, it's nice to have perfection.
0:50:35.815 --> 0:50:40.685
John Williams
We don't in anything and also at meetings we can sit and argue.
0:50:40.695 --> 0:51:6.325
John Williams
We argue after after presentations, but what you're seeing is a consensus on this panel that this is a test that is critically important, being utilized more and more and more by clinicians, people that are responsible for the patients in front of them, people that are responsible for your Medicare insured and this is critical information and those that were skeptics have become found that it is incredibly powerful.
0:50:52.875 --> 0:50:53.145
Alastair Thompson
You.
0:51:6.395 --> 0:51:17.285
John Williams
So I just want to share that that we've got a panel and we've got great diverse input, but it's important to note that this is not just some component of part of it.
0:51:17.295 --> 0:51:24.905
John Williams
This is a critical this is a leap forward in my opinion, and many people's feelings about this Oncotype was not period.
0:51:25.235 --> 0:51:25.935
John Williams
This one is.
0:51:25.935 --> 0:51:26.225
Gabriel Bien-Willner
OK.
0:51:26.235 --> 0:51:26.675
Gabriel Bien-Willner
Thank you.
0:51:26.685 --> 0:51:27.885
Gabriel Bien-Willner
Uh, let's continue.
0:51:27.895 --> 0:51:29.585
Gabriel Bien-Willner
First of all, I would just say I'm not sure I could.
0:51:30.465 --> 0:51:43.295
Gabriel Bien-Willner
I could summarize this as a consensus, but I I do believe that you the fact that you all are having this heated discussion on this call really justifies why we had this meeting in the 1st place.
0:51:43.305 --> 0:51:48.615
Gabriel Bien-Willner
Because as we reviewed the guidelines, we were also very confused as to how this would be handled.
0:51:46.45 --> 0:51:46.185
Alastair Thompson
Yeah.
0:51:48.625 --> 0:51:54.555
Gabriel Bien-Willner
So let's move on to the third question and a lot of these like we're going to find that we've already discussed.
0:51:55.45 --> 0:52:11.505
Gabriel Bien-Willner
But again, back to these variables and understanding what is sufficient, what moves the needle forward, what is a reasonable risk of IB, TR, or whatever other the metric is to warrant a BCS only treatment in DCIS in the Medicare population.
0:52:11.955 --> 0:52:22.245
Gabriel Bien-Willner
What is a reasonable risk reduction that would result in a change in recommendation from BC BCS plus RT to just BCS or BCT to BCS?
0:52:22.535 --> 0:52:33.485
Gabriel Bien-Willner
What variables should be considered if I as a as a as an independent observer have to determine you know to something to be reasonable and necessary?
0:52:33.535 --> 0:52:38.145
Gabriel Bien-Willner
What it has to it has to derive the the patient has to derive some benefit.
0:52:38.155 --> 0:52:41.745
Gabriel Bien-Willner
We've talked about, we've talked about changing management, OK?
0:52:41.755 --> 0:52:43.995
Gabriel Bien-Willner
And I will tell you that that is not sufficient.
0:52:44.635 --> 0:52:48.805
Gabriel Bien-Willner
It's not changing management, it's changing bandit management to benefit the patient.
0:52:49.915 --> 0:52:50.75
Kimberly Van Zee
Yeah.
0:52:50.15 --> 0:52:54.445
Gabriel Bien-Willner
How do I how do I view that delta?
0:52:54.535 --> 0:52:55.205
Gabriel Bien-Willner
What is?
0:52:55.275 --> 0:53:2.925
Gabriel Bien-Willner
What would you guys, as experts, if you know, don't take any specific patient into consideration, but you're general patient population.
0:53:3.905 --> 0:53:6.215
Gabriel Bien-Willner
If you were in, forget the current Test.
0:53:6.225 --> 0:53:9.95
Gabriel Bien-Willner
Forget the specifics of one of these Services.
0:53:9.105 --> 0:53:11.965
Gabriel Bien-Willner
Think about you've got a low-risk patient.
0:53:12.115 --> 0:53:13.565
Gabriel Bien-Willner
What is a low-risk patient?
0:53:13.575 --> 0:53:16.865
Gabriel Bien-Willner
You have a low-risk patient in some thing says I.
0:53:16.875 --> 0:53:32.5
Gabriel Bien-Willner
Can identify a low-risk patient with 5% uh that uh greater confidence that they will not respond to therapy or that they will not benefit from our T what?
0:53:32.15 --> 0:53:33.865
Gabriel Bien-Willner
What are those thresholds that should be looking at?
0:53:33.875 --> 0:53:36.395
Gabriel Bien-Willner
Or am I wrong to even think that there are such thresholds?
0:53:37.225 --> 0:53:38.815
Eileen P. Connolly
I think I can just.
0:53:39.345 --> 0:53:42.835
Eileen P. Connolly
I think it's important to think about what you're talking about.
0:53:42.845 --> 0:53:52.875
Eileen P. Connolly
If you're talking relative risk reduction, and right now if we just look at clinical pathologic features, it's a 50% relative risk reduction, no matter who you are.
0:53:52.965 --> 0:53:55.415
Eileen P. Connolly
The issue is what your baseline risk is.
0:53:55.465 --> 0:54:8.895
Eileen P. Connolly
So if it's 3% at five years and I can make it 1 1/2%, that doesn't mean a lot if you're 95 and have heart failure, if you're 65 and I'm going to take you from 5 to 2% at five years.
0:54:8.905 --> 0:54:12.535
Eileen P. Connolly
But then they're going to live in another 10 or 15 years and it continues to go up.
0:54:12.545 --> 0:54:19.835
Eileen P. Connolly
It doesn't plateau, so it 15 years you're looking at 1520% and now I'm taking it down to 6%.
0:54:19.935 --> 0:54:20.885
Eileen P Connolly
That's meaningful.
0:54:20.895 --> 0:54:27.585
Eileen P. Connolly
So it kind of depends on who you are and where you're threshold of tolerance is.
0:54:27.595 --> 0:54:41.205
Eileen P. Connolly
But then I think what's important is if we can do it too, we have a tool that helps pick out somebody who the relative risk reduction instead of being 50% is 10% and now the benefits really these curves don't separate.
0:54:41.215 --> 0:54:44.515
Eileen P. Connolly
Then it becomes interesting, but that's just my take on this.
0:54:44.665 --> 0:54:45.585
Eileen P. Connolly
I'll let somebody else jump in.
0:54:44.995 --> 0:54:45.315
Alastair Thompson
Hmm.
0:54:45.125 --> 0:55:0.175
Gabriel Bien-Willner
We can I follow up on that and say, OK, so you have 50% relative risk reduction, let's say the other tool is 45% relative risk reduction, at which point and Sir, 10%, OK, is there some?
0:54:47.635 --> 0:54:47.875
Eileen P. Connolly
Sure.
0:55:0.225 --> 0:55:1.595
Gabriel Bien-Willner
Is there some value?
0:55:1.605 --> 0:55:3.75
Gabriel Bien-Willner
Is there something where you'd say you know, what?
0:55:3.895 --> 0:55:5.245
Gabriel Bien-Willner
If it's greater than, if it.
0:55:5.255 --> 0:55:10.565
Gabriel Bien-Willner
If the difference in relative risk reduction is less than some amount, it's probably not meaningful.
0:55:11.255 --> 0:55:18.685
Eileen P. Connolly
You could give me a tool that could tell me who is gonna have a less than 10% risk or a relative risk reduction of 10%.
0:55:18.695 --> 0:55:26.525
Eileen P. Connolly
I would want to use the tool cause what I'm telling you is right now ready everyone radiation reduces the risk by 50%.
0:55:26.595 --> 0:55:39.665
Eileen P. Connolly
That's the relative risk reduction you have to decide what the risk is, but if you had a tool to tell me, oh, for this patient, that radiation risk reduction is 5%, that's a tool like wanna use because I don't have a way to figure it out.
0:55:40.865 --> 0:55:46.15
Eileen P. Connolly
And so that's what I think we're all arguing about is, do we believe this tool can do that or not?
0:55:41.65 --> 0:55:41.305
Alastair Thompson
Yeah.
0:55:46.665 --> 0:55:47.225
Eileen P. Connolly
Umm.
0:55:47.425 --> 0:55:51.475
Eileen P Connolly
And then you have with the patient, you make the decision about.
0:55:51.525 --> 0:55:54.355
Eileen P. Connolly
Am I gonna treat them or not right now?
0:55:54.405 --> 0:55:57.295
Eileen P. Connolly
I mean, everybody gets a 50% risk reduction.
0:55:57.405 --> 0:56:4.155
Eileen P. Connolly
So a lot of patients want radiation, even patients who I'm like probably don't need it because you're not gonna live long enough.
0:56:4.265 --> 0:56:6.415
Eileen P. Connolly
That's not something somebody wants to, you know what I mean?
0:56:6.425 --> 0:56:10.125
Eileen P. Connolly
That's not an easy discussion, so it's at.
0:56:9.865 --> 0:56:16.555
Alastair Thompson
Yeah, we need to get down to about a 5% risk to to, to, to really be talking about things.
0:56:10.175 --> 0:56:11.315
Atif Khan
And I'm gonna take a.
0:56:16.665 --> 0:56:29.95
Alastair Thompson
I guess with a background also an invasive breast cancer where there are now some very good tools that mammaprint the Oncotype, the various Site tool to to try and help us guide risk.
0:56:22.895 --> 0:56:23.165
Eileen P. Connolly
You mean?
0:56:29.155 --> 0:56:36.375
Alastair Thompson
It's about that shared decision making and for invasive breast cancer, not the topic of discussion here in the bad old days.
0:56:36.385 --> 0:57:1.385
Alastair Thompson
We used to just give everybody everything because we weren't really able to discriminate who might not benefit and who would benefit and what we've learned in that world, which is 10 to 20 years ahead of the DCIS world is that by deploying a molecular type assay, we can actually guide and guide with a view to improving not just our patients outlook, but the survival in the invasive setting.
0:57:4.635 --> 0:57:5.775
Alastair Thompson
John, you're mute still.
0:57:4.645 --> 0:57:6.605
Eileen P. Connolly
Oh you're mute.
0:57:7.815 --> 0:57:11.365
John Williams
And the harms we did forgiving everyone.
0:57:11.375 --> 0:57:17.235
John Williams
Chemotherapy with a total of 3% survival benefit were immeasurable.
0:57:13.245 --> 0:57:13.375
Alastair Thompson
Yeah.
0:57:15.365 --> 0:57:15.545
Alastair Thompson
Yeah.
0:57:17.285 --> 0:57:18.235
John Williams
Unspoken.
0:57:18.245 --> 0:57:20.595
John Williams
We never talk about it, harm.
0:57:20.605 --> 0:57:24.835
John Williams
So many people financially, personally, side effects permanently.
0:57:24.845 --> 0:57:48.35
John Williams
Some people die because of that, and when we come back to this, it's no, it's less so the 910% or 5%, I believe 510% is too high, but more importantly, who can we not treat and give the side effects and the harms and the cost and the long term sequella, which is not insignificant for radiation for breast cancer.
0:57:48.325 --> 0:57:51.895
John Williams
And you see that's where this is such a difficult discussion.
0:57:51.905 --> 0:57:58.85
John Williams
And This is why it's a great panel and having everyone involved is that these decisions are personal.
0:57:58.805 --> 0:58:7.165
John Williams
But when we can identify those that do not within a with a heightened sense of certainty, including the nomogram and so on and so forth. But.
0:58:8.975 --> 0:58:17.925
John Williams
We can avoid those harms that we did to thousands, if not hundreds of thousands of people who got chemotherapy that never needed it.
0:58:18.295 --> 0:58:24.865
John Williams
In addition, we can find people that we're not going to withhold radiation and give them radiation.
0:58:27.135 --> 0:58:30.405
John Williams
And save their life for Preisler chance.
0:58:30.415 --> 0:58:34.785
John Williams
I'm having a recurrence or invasive cancer, so that is important and thanks for bringing that up.
0:58:34.795 --> 0:58:35.145
John Williams
Alastair
0:58:35.155 --> 0:58:45.885
John Williams
Is that the harms of radiation are significant and the most sophisticated care that we can give anyone, including the citizens of this country, and that's the nature of this discussion.
0:58:46.115 --> 0:58:47.815
John Williams
It's Medicare we're talking about.
0:58:47.705 --> 0:58:47.855
Alastair Thompson
Yeah.
0:58:47.825 --> 0:58:54.895
John Williams
The citizens of our country, we're making big policy decisions here and you guys do an important job, as you well know, not given the credit.
0:58:55.945 --> 0:58:57.815
Alastair Thompson
I see a very good question.
0:58:56.815 --> 0:58:58.315
John Williams
I don't eat those people well.
0:58:59.375 --> 0:59:0.665
Alastair Thompson
Sorry, sorry to interrupt you, John.
0:59:0.675 --> 0:59:5.305
Alastair Thompson
I see a very good point in the meeting chat about saying radiotherapy is not the same as chemotherapy.
0:59:5.315 --> 0:59:6.85
Alastair Thompson
Absolutely.
0:59:6.495 --> 0:59:17.755
Alastair Thompson
So the side effects are radiotherapy and forgive me I'm not a radiation oncologist, so at if you may want to send me a rude message at some point as a radiation oncologist but.
0:59:18.15 --> 0:59:18.585
Atif Khan
And Eileen.
0:59:18.295 --> 0:59:19.805
Alastair Thompson
And you know what?
0:59:19.815 --> 0:59:28.825
Alastair Thompson
What we see from the evidence is the Oxford overview is saying that there is no safe lower dose to radiation, at least in the breast radiotherapy trials.
0:59:28.835 --> 0:59:32.65
Alastair Thompson
In terms of heart damage, we can see lung cancers.
0:59:32.75 --> 0:59:33.625
Alastair Thompson
We can see it's official cancers.
0:59:33.635 --> 0:59:42.25
Alastair Thompson
We can see sarcomas angiosarcoma as we can see much more common than all of those things which tend to occur 51020 years afterwards.
0:59:42.235 --> 0:59:47.665
Alastair Thompson
We can see the breast fibrosis so we can see the skin changes the telangiectasia.
0:59:47.755 --> 0:59:52.15
Alastair Thompson
We can see the leather effect of to the older effect.
0:59:49.875 --> 0:59:52.265
John Williams
Chronic pain and quality of life.
0:59:52.655 --> 0:59:55.145
John Williams
Chronic pain is rampant.
0:59:52.975 --> 0:59:53.115
Atif Khan
Yeah.
0:59:52.975 --> 0:59:53.215
Alastair Thompson
Yeah.
0:59:54.625 --> 0:59:57.435
Alastair Thompson
So and I'm absolutely.
0:59:55.295 --> 0:59:56.95
John Williams
I see these patients.
0:59:55.725 --> 0:59:57.185
Atif Khan
I yeah, I think.
0:59:57.445 --> 1:0:0.915
Alastair Thompson
I'm not here to knock radiotherapy, so forgive me Atif, but give me Eileen.
0:59:59.245 --> 0:59:59.475
Atif Khan
Yeah.
1:0:1.105 --> 1:0:7.915
Alastair Thompson
But I think just recognizing that if that's the cost for somebody to be disease free in the breast maybe OK.
1:0:7.985 --> 1:0:15.965
Alastair Thompson
But if they've had that radiotherapy and we have a test that could have said you don't need that radiation therapy, that's what's driving me to be here today.
1:0:16.945 --> 1:0:18.555
Atif Khan
Yeah, I think they
1:0:17.475 --> 1:0:20.955
Kimberly Van Zee
And we all agree we want to test.
1:0:21.15 --> 1:0:24.855
Kimberly Van Zee
That would say that there was no radiation benefit.
1:0:24.905 --> 1:0:31.375
Kimberly Van Zee
I don't think we have that test the the hazard ratios referred to the reduction in risk.
1:0:33.35 --> 1:0:39.245
Kimberly Van Zee
By radiation in their low-risk group, their elevated risk group are not statistically significantly different.
1:0:39.435 --> 1:0:43.85
Kimberly Van Zee
They're numerically different, but they're not statistically significantly different.
1:0:43.515 --> 1:0:53.835
Kimberly Van Zee
So it sounds good and that's our goal, but I don't think we've achieved it and just in terms of the question for a patient, I think and I'm gonna give an example.
1:0:53.845 --> 1:0:56.575
Kimberly Van Zee
I had a patient that I thought had a very high risk of recurrence.
1:0:56.705 --> 1:0:58.655
Kimberly Van Zee
50% really high.
1:0:58.665 --> 1:1:1.895
Kimberly Van Zee
She had lots of risk factors, and I told her 50% she goes.
1:1:1.905 --> 1:1:7.155
Kimberly Van Zee
Oh, that's pretty good 5050 where another patient, you might say 10% and she go.
1:1:7.165 --> 1:1:8.895
Kimberly Van Zee
Ohh that's too high.
1:1:8.905 --> 1:1:9.935
Kimberly Van Zee
I want radiation.
1:1:10.65 --> 1:1:13.535
Kimberly Van Zee
So there really is a different value judgment in different personalities.
1:1:13.545 --> 1:1:26.315
Kimberly Van Zee
There's risk averse people and risk tolerant people, and so it's, I can't say I mean after doing this for 30 years, I feel like I cannot judge for an individual person anymore because people are so different in their judgments.
1:1:27.535 --> 1:1:30.15
Alastair Thompson
They are, but we need help, sorry.
1:1:27.595 --> 1:1:28.835
Atif Khan
Yeah, this this goes.
1:1:29.485 --> 1:1:42.255
Atif Khan
This goes back to, yeah, if I may go back to the original question that was posed by Doctor Brian Wolner I, and this is a little bit, you know, like opinion or let's say experts sort of opinion.
1:1:42.265 --> 1:1:45.235
Atif Khan
Let's say you asked like what is the?
1:1:45.345 --> 1:1:46.955
Atif Khan
How would we define low risk?
1:1:46.965 --> 1:1:47.795
Atif Khan
What's the threshold?
1:1:47.805 --> 1:2:2.185
Atif Khan,
And I think I would venture to say that on average clearly it's different on the Upper East Side versus, you know, somewhere else in the world maybe, but about 15% for recognizing the DCIS is not life threatening, recognizing that the salvage therapies are very successful.
1:2:2.195 --> 1:2:9.165
Atif Khan
You know for IBR, I would say I would characterize 15% as sort of the upper limit of IB TR.
1:2:9.175 --> 1:2:14.635
Atif Khan
That would generally be considered acceptable by physicians and by patients.
1:2:15.565 --> 1:2:21.895
Atif Khan
I think if you were to have that down to the 5 to 7% range within assay that would be valuable.
1:2:21.965 --> 1:2:30.415
Atif Khan
I think that would be a meaningful addition and I think that would warrant, you know use, you know utilization of of such an assay.
1:2:34.475 --> 1:2:48.345
Gabriel Bien-Willner
Thank you for answering my question with numbers that you know I I think that's always important for us as we're looking at making decisions in Policy, it's easier for it when you get too money, squishy Answers.
1:2:48.355 --> 1:2:51.15
Gabriel Bien-Willner
It's hard to to really come up with.
1:2:51.795 --> 1:2:55.125
Gabriel Bien-Willner
Frameworks around it but look at with the Group.
1:2:55.215 --> 1:2:55.695
Gabriel Bien-Willner
Agree.
1:2:57.285 --> 1:2:57.755
Gabriel Bien-Willner
You know what?
1:2:57.765 --> 1:3:3.725
Gabriel Bien-Willner
Let me just let me punch this cause I'm actually going to ask this in this next question.
1:3:4.155 --> 1:3:7.485
Gabriel Bien-Willner
Can we just move to the next question, which really will tie to this?
1:3:8.495 --> 1:3:9.985
Gabriel Bien-Willner
I'm so it says.
1:3:9.995 --> 1:3:22.825
Gabriel Bien-Willner
Uh studies have shown that clinical factors such as negative margins, tumor size of less than two or 2.5 centimeters, depending on the Study, lack of committed necrosis and tamoxifen use, are associated with lower IBR.
1:3:24.425 --> 1:3:29.415
Gabriel Bien-Willner
Why is there no consensus on defining what low risk is?
1:3:30.325 --> 1:3:34.495
Gabriel Bien-Willner
What a low-risk population is based on on those factors.
1:3:34.685 --> 1:3:37.155
Gabriel Bien-Willner
How would you define low risk?
1:3:37.165 --> 1:3:43.435
Gabriel Bien-Willner
And it sounds like Doctor Kahn, you you would say that you would define a low-risk population at 15%.
1:3:44.415 --> 1:3:48.285
Gabriel Bien-Willner
Uh, relative or of risk of IB?
1:3:47.275 --> 1:3:52.385
Atif Khan
I absolute absolutely risk of, yeah, absolute absolute risk of IB.
1:3:48.295 --> 1:3:50.915
Gabriel Bien-Willner
TR maybe absolutely risk.
1:3:52.395 --> 1:3:52.875
Atif Khan
TR. Yeah.
1:3:53.785 --> 1:4:2.975
Gabriel Bien-Willner
And then it sounds like you would also say that if you could then reduce risk down to 5%, that would be important.
1:4:3.25 --> 1:4:11.275
Gabriel Bien-Willner
So that there's a substantial relative risk reduction, but once you're below 5%, maybe there's no, there isn't anymore significance.
1:4:11.285 --> 1:4:18.735
Gabriel Bien-Willner
So let's say let's say you you knew the patient was at 5% risk and now you can lower them to 2.5%.
1:4:18.865 --> 1:4:26.555
Gabriel Bien-Willner
Would there be any clinical significance to that, aside from sort of what people feel, right.
1:4:22.105 --> 1:4:24.15
Atif Khan
Probably not, no, I think Jen.
1:4:24.445 --> 1:4:24.605
Atif Khan
Yeah.
1:4:26.255 --> 1:4:28.475
Atif Khan
No, I think generally we would feel that, yeah.
1:4:27.65 --> 1:4:28.365
Gabriel Bien-Willner
OK, so I think what?
1:4:29.495 --> 1:4:29.805
Gabriel Bien-Willner
OK.
1:4:29.815 --> 1:4:35.255
Gabriel Bien-Willner
So those those are real numbers that were thrown out 15% absolute risk.
1:4:34.455 --> 1:4:35.785
Eileen P. Connolly
15 is high.
1:4:35.795 --> 1:4:37.375
Eileen P. Connolly
I mean, just to throw up.
1:4:36.505 --> 1:4:42.315
Atif Khan
I'm getting there from 9804 almost because, you know that's sort of what it was in 9804 and that the.
1:4:37.895 --> 1:4:38.135
Gabriel Bien-Willner
OK.
1:4:41.735 --> 1:4:43.625
Eileen P. Connolly
I mean, at 10 years of this 10%.
1:4:43.675 --> 1:4:45.575
Eileen P. Connolly
So we are like, yeah, 10.
1:4:44.465 --> 1:4:49.715
Gabriel Bien-Willner
But FaceTime done after Connolly let me just throw this out to the group.
1:4:44.485 --> 1:4:45.325
Atif Khan
And right.
1:4:44.655 --> 1:4:45.45
Kimberly Van Zee
Yeah.
1:4:45.95 --> 1:4:47.315
Kimberly Van Zee
And fit 15 years 15%.
1:4:47.865 --> 1:4:48.55
Eileen P. Connolly
Yeah.
1:4:50.785 --> 1:4:55.705
Gabriel Bien-Willner
Please tell me if you agree with those numbers or if you disagree with those numbers or what you what the Group might.
1:4:55.865 --> 1:4:57.775
Gabriel Bien-Willner
If we could come to consensus to what?
1:4:57.785 --> 1:5:6.855
Gabriel Bien-Willner
An absolute relative risk of IB, TR is that would be considered a low-risk patient and added to that.
1:5:8.995 --> 1:5:10.845
Gabriel Bien-Willner
You know, at which point is it no longer?
1:5:12.305 --> 1:5:13.95
Gabriel Bien-Willner
Relevant.
1:5:13.165 --> 1:5:15.115
Gabriel Bien-Willner
What the what?
1:5:15.125 --> 1:5:17.325
Gabriel Bien-Willner
That relative risk reduction is.
1:5:18.255 --> 1:5:32.565
John Williams
I'm going to push back a little bit, you know, this is where, although as you were saying, it's sort of a, a smudgy, this whole topic of DCIS, umm, we talked about that from the very beginning.
1:5:18.385 --> 1:5:18.875
Eileen P. Connolly
You're.
1:5:32.575 --> 1:5:34.385
John Williams
It is a difficult problem.
1:5:35.75 --> 1:5:40.685
John Williams
It is difficult to define and it's not as clear as chemotherapy.
1:5:40.695 --> 1:5:41.615
John Williams
Save your life or not.
1:5:43.835 --> 1:5:47.125
John Williams
However, the what is defines a low risk.
1:5:48.315 --> 1:6:6.565
John Williams
Ultimately, it's decided by different studies and different perceptions and what you're kind of asking also us as the five of us might be individually cause what there's there's no right answer here cause a low risk for a 90-year-old woman is probably 20% to help make a decision.
1:6:6.655 --> 1:6:9.405
John Williams
A low risk for a 50-year-old woman is going to be different.
1:6:9.735 --> 1:6:29.545
John Williams
So one way to do that is to ask the group what they think it is across the board, and I think it because there's no specific answer and it's based on a little bit of clinical practice, if that's what you want to come out with, I would say 5% between 5 and 10% is low risk for your normal population.
1:6:30.295 --> 1:6:32.755
John Williams
Umm, I'll pass that off to Kim.
1:6:32.765 --> 1:6:37.495
John Williams
What do you what what would you define as a low risk for you just in general practice?
1:6:37.615 --> 1:6:49.545
Kimberly Van Zee
Yeah, I mean, I I agree it depends on the patient's because the older you are in the lower your life expectancy, the higher the risk you can tolerate without needing to do radiation or anything, right?
1:6:49.555 --> 1:6:50.675
Kimberly Van Zee
Because the chances of you being.
1:6:49.605 --> 1:6:51.615
Atif Khan
We're talking without radiation right now, right?
1:6:51.675 --> 1:6:53.705
Atif Khan
Just to be clear, we're talking about that radiation.
1:6:51.685 --> 1:6:52.195
Kimberly Van Zee
Yeah. Yeah, yeah.
1:6:51.935 --> 1:6:57.485
John Williams
Correct, but what would you say for the general population if we don't set subset?
1:6:53.225 --> 1:6:53.715
Kimberly Van Zee
Yeah.
1:6:53.715 --> 1:6:53.985
Atif Khan
Yeah, OK.
1:6:53.725 --> 1:6:54.775
Kimberly Van Zee
So if you have it.
1:6:57.65 --> 1:6:59.975
Kimberly Van Zee
Of Medicare patients, right.
1:6:59.515 --> 1:7:1.645
John Williams
No, let's just talk across the board where we haven't.
1:6:59.985 --> 1:7:1.555
Kimberly Van Zee
Which is all over 65.
1:7:1.695 --> 1:7:2.885
John Williams
We haven't defined it that.
1:7:2.895 --> 1:7:4.785
John Williams
What is a sub in gem?
1:7:4.845 --> 1:7:8.275
Kimberly Van Zee
I think this this whole discussion is for Medicare patients.
1:7:9.105 --> 1:7:11.155
Kimberly Van Zee
Dr. Bien-Willner, is that true?
1:7:9.385 --> 1:7:18.715
John Williams
I understand, but also we had the clinical studies are not done on Medicare patients specifically and where we can't even account for what the age is.
1:7:18.725 --> 1:7:25.455
John Williams
Certainly that makes it even more relevant to that situation, but we this first time we brought that up up draw a line.
1:7:25.565 --> 1:7:30.125
John Williams
Kim, if you can on what you would say based on studies is low risk.
1:7:31.725 --> 1:7:39.795
Kimberly Van Zee
Well, we've yeah, you know, we did a study and by decade of age, the risk goes down.
1:7:32.755 --> 1:7:35.175
John Williams
For you in practice, just what do you consider low risk?
1:7:39.805 --> 1:7:47.45
Kimberly Van Zee
The older you get the 10-year risk of recurrence for DCIS controlling for all other factors goes down and your risk of death goes up.
1:7:42.665 --> 1:7:43.395
John Williams
I understand I.
1:7:47.115 --> 1:7:52.305
Kimberly Van Zee
So my what I'm trying to say is my threshold is different depending on the patient in front of me.
1:7:52.375 --> 1:7:55.285
Kimberly Van Zee
I think I agree with that TIF something around 15%.
1:7:55.295 --> 1:8:0.205
Kimberly Van Zee
If you take an average but a young, healthy woman, it might be lower like 10%.
1:8:0.215 --> 1:8:6.145
Kimberly Van Zee
Like Dr. Connolly said, but an older lady like I said, I've had people that say 50% is fine for them.
1:8:6.315 --> 1:8:9.785
John Williams
I understand, but we're we're trying to narrow down what we decide.
1:8:6.805 --> 1:8:12.535
Kimberly Van Zee
So so overall overall, I agree with our chief about 15% overall.
1:8:12.945 --> 1:8:13.85
John Williams
Yeah.
1:8:13.185 --> 1:8:28.245
Kimberly Van Zee
But I think that's a very important caveat in making any decision is the older you are and the fewer years of life ahead of you the fewer years you have to have a recurrence and the lower your per year risk is.
1:8:28.545 --> 1:8:30.915
John Williams
I think we have consensus on that, Eileen.
1:8:30.925 --> 1:8:32.5
John Williams
What's your?
1:8:32.185 --> 1:8:32.855
John Williams
What's your tech?
1:8:33.25 --> 1:8:37.985
John Williams
Where would you say can you draw it for the general, assuming that there are caveats, really young, really old.
1:8:39.15 --> 1:8:41.145
Eileen P. Connolly
I mean, I think those things are true.
1:8:41.155 --> 1:8:51.85
Eileen P. Connolly
I think the hard part is they're if you consistently tell somebody you're gonna get a 50% reduction in whatever that risk is that I'm estimating for you.
1:8:51.575 --> 1:8:59.285
Eileen P. Connolly
If it you know without radiation, a lot of people with modern radiation and minimal toxicity, I mean we can give it in one week.
1:8:59.355 --> 1:9:0.725
Eileen P. Connolly
Are you gonna take radiation.
1:9:1.85 --> 1:9:3.465
Eileen P. Connolly
So that's the thing right now.
1:9:1.575 --> 1:9:1.845
Alastair Thompson
Umm.
1:9:3.515 --> 1:9:9.645
Eileen P Connolly
I can see a 7-year-old and offer her one week of treatment and she's gonna say, well, you're gonna reduce it by 50%.
1:9:9.745 --> 1:9:10.475
Eileen P. Connolly
That's easy.
1:9:10.585 --> 1:9:11.225
Eileen P. Connolly
One week is easy.
1:9:12.75 --> 1:9:14.85
Eileen P. Connolly
That's where everything is changed.
1:9:13.265 --> 1:9:14.785
Atif Khan
Yeah, I agree with that.
1:9:14.235 --> 1:9:18.785
Eileen P. Connolly
So you know, a lot of women are choosing radiation.
1:9:18.915 --> 1:9:25.725
Eileen P. Connolly
Nothing that we use clinical Pathologic tells me how much benefit they're going to get, because every trial shows a 50% reduction.
1:9:26.595 --> 1:9:28.345
Eileen P. Connolly
So it's yeah.
1:9:26.735 --> 1:9:28.805
Kimberly Van Zee
Another way to to present it.
1:9:28.815 --> 1:9:34.305
Kimberly Van Zee
Sometimes it helps is is when I say it's 90% you have a 90% chance of it not coming back.
1:9:34.315 --> 1:9:36.425
Kimberly Van Zee
And if you do radiation, it's 95.
1:9:36.575 --> 1:9:40.445
Kimberly Van Zee
Sometimes just flipping, I know, but. But.
1:9:36.725 --> 1:9:39.195
Eileen P. Connolly
Yeah, but they still feared the 5% different.
1:9:39.205 --> 1:9:42.505
Eileen P. Connolly
I mean like that's I I do the same thing and that's fine.
1:9:41.915 --> 1:9:47.325
Kimberly Van Zee
But it's funny when I just say it that way, they go along with it much better than saying at the five and 10.
1:9:47.335 --> 1:9:48.505
Kimberly Van Zee
If you say 90%.
1:9:47.575 --> 1:9:54.585
Eileen P. Connolly
I will tell you I have a very my patient population is majority minority.
1:9:54.595 --> 1:9:57.515
Eileen P Connolly
If you take something away, they wanna know.
1:9:57.575 --> 1:9:59.825
Eileen P. Connolly
They feel like you're taking it away from them.
1:10:0.55 --> 1:10:0.975
John Williams
And we can't do that in.
1:10:0.335 --> 1:10:4.325
Eileen P. Connolly
That's a really different like, it's not as easy as that.
1:10:1.5 --> 1:10:1.185
Atif Khan
Yeah.
1:10:4.335 --> 1:10:6.525
Eileen P. Connolly
They're gonna be like, look, it's one week of treatment.
1:10:6.535 --> 1:10:7.805
Eileen P. Connolly
I want it period.
1:10:6.605 --> 1:10:8.615
Atif Khan
Yeah, I think there is.
1:10:7.705 --> 1:10:9.395
John Williams
Alistair trying or?
1:10:8.785 --> 1:10:13.15
Atif Khan
There is not a lot of, there's not a whole lot of fear around radiation.
1:10:13.25 --> 1:10:29.785
Atif Khan
I know we we're alluding to the side effects earlier, but from the patient perspective, there are quite accepting a radiotherapy and I think there is a culture, paradoxically there is a culture if you're around Bcis cuz the carcinoma in the way that we call it and you know we're all partly to blame for that.
1:10:14.5 --> 1:10:17.885
Eileen P. Connolly
Uh, it's so well tolerated now.
1:10:15.645 --> 1:10:15.835
Alastair Thompson
You.
1:10:27.785 --> 1:10:27.965
Alastair Thompson
Yeah.
1:10:29.795 --> 1:10:30.375
Atif Khan
But there is a.
1:10:30.385 --> 1:10:42.835
Atif Khan
So, you know, I think when you pose this choice of, you know, doing everything they can to minimize their chance of recurrence versus leaving something on the table, they almost always do opt for, you know, receipt of radiotherapy.
1:10:43.215 --> 1:10:44.705
Eileen P. Connolly
Yeah, they do, I mean.
1:10:44.155 --> 1:10:45.265
John Williams
Alistair Witcher tick.
1:10:45.635 --> 1:10:45.895
Kimberly Van Zee
Well.
1:10:46.185 --> 1:10:46.535
Alastair Thompson
Yeah.
1:10:46.545 --> 1:10:50.915
Alastair Thompson
So my apologies to Atif and Eileen for being rude about the side effects of radiotherapy.
1:10:50.925 --> 1:10:52.105
Alastair Thompson
You're absolutely right.
1:10:52.305 --> 1:10:56.255
Alastair Thompson
Things nowadays much more modern, much more directed, much fewer side effects.
1:10:56.265 --> 1:11:2.675
Alastair Thompson
But there is a history that patients sometimes fear radiotherapy, probably inappropriately so.
1:11:2.685 --> 1:11:15.155
Alastair Thompson
In direct answer your question, John, I think 5% is where I'd sit, and I'd sit there because I know that 3% is the cut off for most chemotherapy agents.
1:11:15.725 --> 1:11:18.515
Alastair Thompson
I think 5% is probably a reasonable.
1:11:20.465 --> 1:11:21.655
Alastair Thompson
Position for me to sit.
1:11:21.945 --> 1:11:22.565
Alastair Thompson
Thank you for asking.
1:11:22.5 --> 1:11:24.115
John Williams
Doctor Peladas is on.
1:11:23.705 --> 1:11:24.605
Kimberly Van Zee
But yeah.
1:11:24.165 --> 1:11:25.685
John Williams
And can you hear us or speak?
1:11:30.205 --> 1:11:31.775
John Williams
And can you hear us or unmute?
1:11:30.815 --> 1:11:31.125
Alastair Thompson
Thank you.
1:11:31.255 --> 1:11:35.645
Gabriel Bien-Willner
She cannot speak because I need to turn on her mic and I'm having a hard time finding her.
1:11:31.265 --> 1:11:31.415
Kimberly Van Zee
What?
1:11:36.155 --> 1:11:38.275
Gabriel Bien-Willner
Unfortunately, on the list here.
1:11:36.795 --> 1:11:37.545
John Williams
I don't know 100.
1:11:38.75 --> 1:11:40.405
Kimberly Van Zee
What 11 difference?
1:11:39.495 --> 1:11:40.515
Gabriel Bien-Willner
Uh, apologize.
1:11:41.355 --> 1:11:47.435
Kimberly Van Zee
One difference between chemotherapy you're talking about live saved, where radiation doesn't save lives.
1:11:47.445 --> 1:11:49.625
Kimberly Van Zee
For DCIS, it just prevents recurrence.
1:11:49.635 --> 1:12:6.65
Kimberly Van Zee
So my threshold for saving lives is much lower, meaning I would do chemo for a smaller benefit than radiation to present to prevent a risk of recurrence after DCIS and a breast, because that salvageable, like Atif said.
1:12:6.435 --> 1:12:8.845
Kimberly Van Zee
But you know, life versus.
1:12:7.25 --> 1:12:9.675
Eileen P. Connolly
But salvage is not without cost.
1:12:9.865 --> 1:12:10.915
Kimberly Van Zee
No, no, agreed.
1:12:9.925 --> 1:12:14.365
Eileen P. Connolly
I mean, that's like that's not a small thing for somebody, you know.
1:12:11.5 --> 1:12:11.695
Kimberly Van Zee
Agreed. But.
1:12:13.595 --> 1:12:15.365
Kimberly Van Zee
No, no, I totally agree.
1:12:15.375 --> 1:12:16.695
Kimberly Van Zee
Having a recurrence is Terra.
1:12:16.705 --> 1:12:18.445
Kimberly Van Zee
They hate it, even if it's just ECS.
1:12:18.455 --> 1:12:19.245
Kimberly Van Zee
Ohh I totally agree.
1:12:19.255 --> 1:12:20.265
Kimberly Van Zee
But it's not death.
1:12:20.535 --> 1:12:21.985
Kimberly Van Zee
It's not metastatic disease.
1:12:20.885 --> 1:12:23.875
Atif Khan
That's why we would say 15% and not 50%, right?
1:12:21.105 --> 1:12:21.315
John Williams
Or.
1:12:23.785 --> 1:12:24.955
Kimberly Van Zee
Yeah, yeah.
1:12:23.885 --> 1:12:26.245
Atif Khan
I mean like so it's still, yeah.
1:12:25.15 --> 1:12:25.805
Eileen P. Connolly
Right, I get that.
1:12:25.815 --> 1:12:26.545
Eileen P. Connolly
No, I understand.
1:12:26.555 --> 1:12:30.325
Eileen P. Connolly
But I see the bargain has changed because it's gotten radiation has gotten easier.
1:12:30.455 --> 1:12:32.765
Eileen P. Connolly
It's shorter, there's much less toxicity.
1:12:30.855 --> 1:12:31.15
Alastair Thompson
Yeah.
1:12:33.75 --> 1:12:35.685
Eileen P. Connolly
Everybody is much more willing to do it than they used to be.
1:12:35.695 --> 1:12:37.545
Eileen P. Connolly
It was a different discussion 10 years ago.
1:12:37.615 --> 1:12:40.415
Eileen P Connolly
It really was when you were talking about six weeks, you know.
1:12:37.815 --> 1:12:38.505
Atif Khan
I just want to.
1:12:37.855 --> 1:12:38.445
John Williams
And when you?
1:12:38.615 --> 1:12:43.595
Atif Khan
I wanna be there was a second part to the question, though I think we did.
1:12:43.605 --> 1:12:45.345
Atif Khan
We answer the question that was posed or.
1:12:46.105 --> 1:12:46.875
John Williams
A great question.
1:12:49.175 --> 1:12:49.655
Eileen P. Connolly
You're good.
1:12:50.195 --> 1:12:52.605
Gabriel Bien-Willner
I think I think, let me let me.
1:12:52.615 --> 1:12:55.585
Gabriel Bien-Willner
I think you did and then you went way past it.
1:12:55.595 --> 1:12:57.785
Gabriel Bien-Willner
But you know the the, the, the, the.
1:12:57.795 --> 1:13:8.575
Gabriel Bien-Willner
The problem here is you know, I've read a lot of, we read a lot of papers about this low-risk population, and they all had different cut offs and standards for what that meant.
1:13:8.585 --> 1:13:20.475
Gabriel Bien-Willner
There was no agreement in the literature as to what low risk means, and then the and the guidelines themselves talk about sufficiently low risk without mentioning what that even means.
1:13:21.125 --> 1:13:24.625
Gabriel Bien-Willner
So it's like the deaf leading the blind and trying to decide what that.
1:13:22.325 --> 1:13:22.725
Atif Khan
Yeah, yeah.
1:13:24.595 --> 1:13:25.215
Atif Khan
It is.
1:13:24.675 --> 1:13:25.995
Gabriel Bien-Willner
How do you write Policy?
1:13:26.225 --> 1:13:30.475
Gabriel Bien-Willner
How do you create a A framework around something that has no definition?
1:13:27.355 --> 1:13:27.475
Atif Khan
Yeah.
1:13:30.525 --> 1:13:38.635
Gabriel Bien-Willner
Maybe intentionally so, particularly around things like discussing things with patients that makes it almost impossible for us to have a framework around.
1:13:32.715 --> 1:13:32.875
Alastair Thompson
Yeah.
1:13:38.645 --> 1:13:42.435
Gabriel Bien-Willner
So the goal of the question was to come up with some reasonable.
1:13:42.925 --> 1:13:48.155
Gabriel Bien-Willner
So if you could say, for example, Doctor Williams that you know you can't define what that means, it will be different.
1:13:48.225 --> 1:13:53.975
Gabriel Bien-Willner
The goal is to get a definition and put it in a policy and put a framework around it.
1:13:53.985 --> 1:14:1.995
Gabriel Bien-Willner
And maybe if we put a, maybe it's the six of you, uh, I'd love to hear from Doctor Tuniki.
1:14:2.5 --> 1:14:2.565
Gabriel Bien-Willner
Who hasn't?
1:14:3.585 --> 1:14:7.485
Gabriel Bien-Willner
Opined much here, but uh and doctor pellet if I can get her.
1:14:7.495 --> 1:14:7.745
Gabriel Bien-Willner
Uh.
1:14:7.755 --> 1:14:16.515
Gabriel Bien-Willner
Unmuted I and I think this is just a consequence of her coming in a little later and I can't expand the entire list of people participating, but.
1:14:18.395 --> 1:14:31.855
Gabriel Bien-Willner
You know, if our policy says this is what we define low risk to be and we put in real numbers, then maybe others will follow and maybe those numbers become the numbers and I know that nobody likes that.
1:14:29.765 --> 1:14:30.95
Alastair Thompson
Umm.
1:14:30.235 --> 1:14:30.455
Kimberly Van Zee
How?
1:14:31.485 --> 1:14:31.685
John Williams
Well.
1:14:31.865 --> 1:14:33.705
Gabriel Bien-Willner
But not having standards is also bad.
1:14:34.405 --> 1:14:48.495
Kimberly Van Zee
Would it be possible in in addition to saying, OK, pick a number 15% but have it be within their expected lifetime because again 15% for a 50 year old is different than 15% for a 95 year old.
1:14:39.505 --> 1:14:39.775
Eileen P. Connolly
Uh.
1:14:49.675 --> 1:14:52.715
Kimberly Van Zee
So it that's what we're trying to convey too.
1:14:50.785 --> 1:14:51.605
Gabriel Bien-Willner
Yeah, anything's.
1:14:51.905 --> 1:14:54.375
Gabriel Bien-Willner
Look, I think I think.
1:14:52.915 --> 1:14:55.715
Kimberly Van Zee
So something within their life expectancy?
1:14:56.645 --> 1:14:56.915
Gabriel Bien-Willner
Yeah.
1:14:56.925 --> 1:15:24.475
Gabriel Bien-Willner
If you say 15% in patients who have more than five years of life expectancy or a complicated, you know, algebraic equation that can combines this relative risk or absolute risk with some, you know, age of the patient or, you know, expected life expectancy based on some refined rubric, that's all fine.
1:15:24.525 --> 1:15:26.715
Gabriel Bien-Willner
It doesn't have to be 15% done.
1:15:25.675 --> 1:15:25.965
Eileen P. Connolly
Well, the.
1:15:26.725 --> 1:15:29.45
Gabriel Bien-Willner
It just it's just got to be something.
1:15:27.825 --> 1:15:31.495
Eileen P. Connolly
I E the problem is it doesn't plateau.
1:15:27.945 --> 1:15:28.85
Kimberly Van Zee
Yeah.
1:15:30.75 --> 1:15:30.235
Kimberly Van Zee
Yeah.
1:15:31.505 --> 1:15:33.895
Eileen P. Connolly
It's not 15% as a flat plateau.
1:15:33.905 --> 1:15:35.975
Eileen P. Connolly
I mean, it's 15%, fifteen years.
1:15:34.385 --> 1:15:34.625
Kimberly Van Zee
Right.
1:15:35.985 --> 1:15:48.335
Eileen P. Connolly
It's 20% at 20 years, which is obviously X life expectancy and we we use the enrollment criteria for 9804 for better or worse to roughly categorize somebody as low risk.
1:15:37.855 --> 1:15:38.95
Kimberly Van Zee
Right.
1:15:48.405 --> 1:16:9.945
Eileen P. Connolly
But we know that in that group there was a 90% benefit to radiation, meaning, and if we believed, you know, decision RT in their data set took 9804 like patients and reclassified them, they sorted them out, 40% had high risk and a lot of benefit and the remainder didn't seem to get any benefit from radiation.
1:16:10.115 --> 1:16:12.465
Eileen P. Connolly
So that's where I get a little bit stuck.
1:16:12.475 --> 1:16:20.365
Eileen P. Connolly
Whereas if you set a threshold and then just use clinical pathologic features, you're not picking out, you're not.
1:16:20.375 --> 1:16:21.985
Eileen P Connolly
You're missing that reassortment.
1:16:21.995 --> 1:16:31.45
Eileen P. Connolly
You've lost it, and now there's a lot of people who might not get treated who really benefit and we're probably over treating people who don't like it.
1:16:27.865 --> 1:16:28.15
Atif Khan
Yeah.
1:16:29.115 --> 1:16:33.915
Kimberly Van Zee
But but that data, it was not statistically significantly different.
1:16:30.105 --> 1:16:31.225
Atif Khan
And to that point I I know.
1:16:34.5 --> 1:16:35.15
Kimberly Van Zee
Dr. Connolly.
1:16:35.145 --> 1:16:37.715
Kimberly Van Zee
They it was numerically different, but it wasn't.
1:16:35.435 --> 1:16:36.95
Eileen P. Connolly
I understand.
1:16:37.725 --> 1:16:39.295
Kimberly Van Zee
It could have happened by chance.
1:16:39.305 --> 1:16:40.235
Kimberly Van Zee
In other words, it wasn't.
1:16:40.475 --> 1:16:44.585
Eileen P Connolly
But they did use 3 datasets and I know you're saying, oh, that it was the original cord.
1:16:44.595 --> 1:16:45.105
Eileen P. Connolly
They did.
1:16:45.155 --> 1:16:47.465
Eileen P. Connolly
If you look, it's they're not all the same cohort.
1:16:47.475 --> 1:16:49.625
Eileen P. Connolly
I mean, the Swedish DCIS was a randomized trial.
1:16:47.835 --> 1:16:48.105
Kimberly Van Zee
Yep.
1:16:49.635 --> 1:16:51.25
Eileen P. Connolly
They used the Kaiser Permanente.
1:16:51.35 --> 1:16:53.945
Eileen P. Connolly
They used the Massachusetts data, so those are all independent.
1:16:53.955 --> 1:16:58.385
Eileen P. Connolly
Yes, in the last paper that combined all three, but they were three separate data sets.
1:16:58.395 --> 1:17:1.525
Eileen P. Connolly
You can't tell me you can get the same like I get it.
1:16:59.205 --> 1:16:59.415
Kimberly Van Zee
Right.
1:17:1.75 --> 1:17:6.335
Kimberly Van Zee
No, they did, but they changed their, they changed their tool based.
1:17:1.535 --> 1:17:1.835
Eileen P. Connolly
We need.
1:17:4.685 --> 1:17:6.385
Eileen P. Connolly
They added a second component.
1:17:6.455 --> 1:17:6.595
Eileen P. Connolly
Right.
1:17:7.295 --> 1:17:8.245
Kimberly Van Zee
No, they changed their.
1:17:7.525 --> 1:17:8.885
Eileen P. Connolly
They added a second component.
1:17:7.665 --> 1:17:11.45
John Williams
Uh, Gabe, I'm gonna make a suggestion.
1:17:9.315 --> 1:17:10.845
Kimberly Van Zee
They changed their cut offs too.
1:17:10.745 --> 1:17:11.465
Atif Khan
But what?
1:17:11.95 --> 1:17:13.205
John Williams
Let's let Brian chime in.
1:17:13.215 --> 1:17:14.225
John Williams
He's in the call.
1:17:14.235 --> 1:17:17.505
John Williams
And then why don't you go in the background and try to let Anne in?
1:17:18.375 --> 1:17:20.385
John Williams
So because Anna's been listening in.
1:17:20.395 --> 1:17:24.545
John Williams
But she's an an important participant, and it'd be nice to hear her perspective.
1:17:24.835 --> 1:17:29.525
John Williams
More so, one would let Brian talk and then go through the long list.
1:17:28.135 --> 1:17:28.245
Atif Khan
And.
1:17:29.985 --> 1:17:33.465
Atif Khan
I'll just note that it must be absolute torture to listen to all this and not be able to comment.
1:17:30.985 --> 1:17:31.115
Brian J. Czerniecki
But.
1:17:38.45 --> 1:17:38.965
John Williams
Brian, what are your thought?
1:17:38.65 --> 1:17:46.175
Brian J. Czerniecki
I would say if you asked me, my definition of what I consider low risk, I would say 5%, but that's gotta be tempered by patients.
1:17:46.185 --> 1:17:53.15
Brian J. Czerniecki
And I I think as the decades go by and health changes for patient that's gonna variable.
1:17:54.295 --> 1:18:26.415
Brian J. Czerniecki
I've heard a lot about the argument of using old data, but we're we're starting with RT 908, which is an old Study, and it's based on clinical validation, so I'm not sure if that's a good starting point or not for this whole thing and it kind of reminds me a little bit about the arguments that we've had for the past 50 years about the survival benefit from axillary dissection, where there's probably a very, very, very small marrow group that may benefit from that that we've been trying to tease out.
1:18:23.95 --> 1:18:23.385
Alastair Thompson
Umm.
1:18:26.425 --> 1:18:28.235
Brian J. Czerniecki
And we've never really found that.
1:18:31.755 --> 1:18:37.365
Alastair Thompson
Yeah, that's because we have no molecular assay to tell us who benefits from the axillary dissection, of course.
1:18:38.685 --> 1:18:39.35
Eileen P. Connolly
Exactly.
1:18:42.145 --> 1:18:42.885
John Williams
And are you on?
1:18:42.215 --> 1:18:49.195
Brian J. Czerniecki
You get my point though, because if we had a a a test just like that, we'd be having the same kind of argument right now right now today.
1:18:52.655 --> 1:18:57.985
John Williams
Again, what you speak up and share with us clarity on this, but.
1:18:57.515 --> 1:18:58.285
Anne Peled
I don't know.
1:18:58.295 --> 1:19:0.745
Anne Peled
I know I hope for clarity, but I apologize everyone.
1:19:0.895 --> 1:19:8.825
Anne Peled
I'm in the middle of taking care of people DCIS, but I actually am not only a breast cancer surgeon, but I'm also a patient.
1:19:8.915 --> 1:19:15.365
Anne Peled
I've actually benefited from decision RT testing myself, and to be honest, I appreciate everyone's input so much.
1:19:15.375 --> 1:19:25.645
Anne Peled
But the fact that there aren't patients on here feels really challenging to be completely honest, and I think all of us has breast care providers are very patient focused, right?
1:19:25.655 --> 1:19:33.275
Anne Peled
It's a specialty that really focuses on these complicated decision makings, making conversations with patients, but ultimately the patients get to choose.
1:19:33.605 --> 1:19:41.115
Anne Peled
So, to be honest, I think a 5% chance like higher than that feels definitely into a higher risk category, right.
1:19:41.125 --> 1:19:46.295
Anne Peled
So you tell me 15% or under as low risk as a patient, that sounds way too high to me.
1:19:46.305 --> 1:19:55.935
Anne Peled
And so again, I know this does depend on how much longer people are gonna live, but in my opinion the best thing we can do is give people the information and let them be making these choices.
1:19:55.945 --> 1:19:58.715
Anne Peled
I know someone was saying people are afraid of a radiation.
1:19:58.725 --> 1:20:2.615
Anne Peled
Unfortunately, a lot of people are afraid of radiation still, and I hear that all the time.
1:20:2.865 --> 1:20:9.565
Anne Peled
And again, I think what's so important about this it is gives us real numbers and real data in our clinical situations.
1:20:9.575 --> 1:20:12.805
Anne Peled
You know, it's not someone telling me that cuz I got diagnosed at 37.
1:20:12.815 --> 1:20:14.815
Anne Peled
I 100% need to do all the things right.
1:20:14.825 --> 1:20:15.315
Anne Peled
It's not.
1:20:15.325 --> 1:20:23.75
Anne Peled
It gives you information at all different ages and stages that gives us better information than just guessing based off clinical pathologic features.
1:20:23.85 --> 1:20:34.35
Anne Peled
So again, I just wanted to, for what it's worth, add that I think not taking too into account that the patient should get this information to make their choices feels like the mess in that situation.
1:20:36.855 --> 1:20:38.815
Gabriel Bien-Willner
If I could just comment on that.
1:20:41.455 --> 1:20:44.925
Gabriel Bien-Willner
The goal here is to understand the evidence, right?
1:20:44.935 --> 1:20:59.665
Gabriel Bien-Willner
It understood that the decision is going to be made between the physician and the patient, but we have to with the goal here, is to understand the evidence and practices to determine whether reasonable necessary thresholds are made for coverage, not for you to order tests.
1:20:59.675 --> 1:21:1.125
Gabriel Bien-Willner
You can always order a Test.
1:21:1.505 --> 1:21:5.125
Gabriel Bien-Willner
Nothing that is done here will prevent you from doing that.
1:21:5.555 --> 1:21:14.645
Gabriel Bien-Willner
We're just trying to establish evidentiary thresholds to meet a defined category of covered benefit under the Medicare program.
1:21:16.375 --> 1:21:25.85
Atif Khan
Uh Doctor Brian Wolner I you had, I think, raised the question of like, why can't we use uh comido necrosis in grade and blah blah blah all that stuff.
1:21:25.315 --> 1:21:26.645
Atif Khan
Like, why hasn't that been done?
1:21:26.655 --> 1:21:34.365
Atif Khan
And the answer is that it has been done going all the way back to the Van Nuys prognostic index and also Kim's normal gram.
1:21:34.495 --> 1:21:37.805
Atif Khan
I mean, that expressly was the intention behind those things.
1:21:37.815 --> 1:21:43.435
Atif Khan
And I think kind of what we're talking about here is like, how do we improve further upon that?
1:21:44.545 --> 1:21:45.55
Alastair Thompson
Umm.
1:21:45.395 --> 1:21:46.225
Alastair Thompson
The there's also more.
1:21:45.595 --> 1:21:46.365
Gabriel Bien-Willner
I take it.
1:21:48.115 --> 1:21:48.415
Gabriel Bien-Willner
Go ahead.
1:21:48.305 --> 1:21:52.265
Alastair Thompson
Alright, I was just gonna say there's also been fairly recent evidence.
1:21:52.275 --> 1:22:2.35
Alastair Thompson
Uh Study by Harrison Hotel, for example, and it it essentially 10% of grade one DCIS and 10% of Grade 3 DCIS pathologists will agree on.
1:22:2.45 --> 1:22:43.265
Alastair Thompson
But the other 80%, eight zero percent pathologists, you take 9 international pathology, DCIS superstars, they can't agree on on the grade you look at chamado de process you take 36 different pathologists across the United States, Harrison, Metal Residue Snit they can't agree on what a definition of these uh DCIS committed across this is and you know where we're struggling with these I'm not meaning ill of the pathology community but when it is so difficult to get a standardized grade or comedian across is present or absent to very basic things it just means we need something better.
1:22:43.525 --> 1:22:45.495
Alastair Thompson
To guide our shared decision making.
1:22:46.625 --> 1:22:57.675
Gabriel Bien-Willner
Well, I first want to say thank you for introducing a new piece of evidence that wasn't likely listed in the bibliography for this and will happily take that back and and review that publication as well.
1:22:58.205 --> 1:23:10.375
Gabriel Bien-Willner
I do want to know knowing that we have about 30 minutes left, I do want to hit some of these final final points and also I want to comment that Doctor Khan seems to constantly be wanting to jump to the next question and maybe by design.
1:23:10.625 --> 1:23:12.295
Gabriel Bien-Willner
So thank you for that comment.
1:23:12.305 --> 1:23:17.325
Gabriel Bien-Willner
Let's jump to the next question, which you know is to the point that you raised.
1:23:17.625 --> 1:23:41.235
Gabriel Bien-Willner
I'm are the Van Nuys prognostic index, the MSK nomogram, the the patient prognostic score, and if you want to consider the MD Anderson Nomograms, which I I understand are for invasive cancer, but I've also heard that people use this and to disable settings as well are those accepted and currently used means of risk stratifying diseased patients.
1:23:41.805 --> 1:23:44.75
Gabriel Bien-Willner
One, what are the known limitations?
1:23:44.85 --> 1:23:47.75
Gabriel Bien-Willner
And two, why are these not broadly implemented?
1:23:50.815 --> 1:23:53.345
Gabriel Bien-Willner
I'm assuming they're not proudly implemented in the question.
1:23:53.725 --> 1:23:54.375
Alastair Thompson
No, they're not.
1:23:54.385 --> 1:23:58.75
Alastair Thompson
They're rarely used outside the institutions that designed them.
1:23:58.485 --> 1:24:10.195
Alastair Thompson
And then use originally generated in a pre breast screening era when DCIS was very different large palpable areas of DCIS not really applicable.
1:24:10.635 --> 1:24:24.175
Alastair Thompson
And as you may or may not know, I was a MD Anderson employee for a very happy five years and we did not use the the nomograms either for invasive and certainly not for DCIS am.
1:24:24.255 --> 1:24:35.715
Alastair Thompson
I haven't recently visited Memorial, but those nomograms worthy don't only be and and forgive me for saying this Kimberly and and not widely used in the United States.
1:24:35.725 --> 1:24:54.255
Alastair Thompson
Never mind further afield, and I think all these things demonstrate that there's a crying need to have something that is standard that we can rely on that is, is, is validated and tested widely on populations in Australia, as has been done in the United States.
1:24:54.445 --> 1:24:58.5
Alastair Thompson
Has this been done in a randomized trial from Sweden, as has been done?
1:24:58.255 --> 1:25:7.185
Alastair Thompson
You know, it's just a body of evidence which is pointing to us, as John Williams was saying earlier to just thinking, is now the time to make this standard.
1:25:8.455 --> 1:25:25.965
John Williams
I I I'll kind of pick you back with that a little bit in that just and and Kim, I'll also be quick is that you know we're using criteria that go back 20-30 years and for the ones that you list and they were very helpful, they were leaps forward from 30-40 years ago.
1:25:8.765 --> 1:25:10.165
Kimberly Van Zee
Be, you know, didn't.
1:25:26.795 --> 1:25:38.555
John Williams
But once we've started using genomic assays, for example, for invasive cancer and for other cancers, all of a sudden it's a leap forward you can individualize and prioritize and individualized care.
1:25:39.335 --> 1:25:39.735
John Williams
Umm.
1:25:40.15 --> 1:25:54.975
John Williams
Also, all of these what's kind of unique in the conflict here is that the nomogram and then a Van Nuys criteria and like for example, a decision RT pulls out out of all the low risk molecular.
1:25:55.25 --> 1:25:55.475
John Williams
Excuse me?
1:25:55.485 --> 1:25:58.565
John Williams
Low risk memorial nomogram patients.
1:25:58.575 --> 1:26:2.695
John Williams
It pulls out 30 to 40% that are biologically high risk based on their tests.
1:26:2.845 --> 1:26:12.595
John Williams
So we have tests and scales that are all little different and conflicting, but ultimately there has to be and we have to use that information.
1:26:12.685 --> 1:26:29.785
John Williams
We cannot ethically say we're not gonna use a genomic assay if we feel that it's gonna be helpful, but most importantly, you have, we have to have trust in the treating physicians to use what applies to individual patients.
1:26:29.855 --> 1:26:35.445
John Williams
And actually I don't order these tests on people that it doesn't apply to or it's a waste of resources.
1:26:35.595 --> 1:26:38.525
John Williams
And there's that's what we're also not talking about.
1:26:38.735 --> 1:26:42.405
John Williams
We can kind of pull the things that also are helpful.
1:26:42.465 --> 1:26:45.465
John Williams
It does not apply to everyone, just like a recurrence.
1:26:45.555 --> 1:26:56.235
John Williams
A local recurrence without radiation of 7% doesn't apply for everyone, but the problem is, all of these scales conflict with one another, but I do believe that this is where we're going.
1:26:56.705 --> 1:26:57.895
John Williams
Kim, back to you.
1:26:57.855 --> 1:26:58.205
Kimberly Van Zee
Yeah.
1:26:57.905 --> 1:26:58.405
John Williams
Sorry about that.
1:26:58.215 --> 1:27:8.705
Kimberly Van Zee
But I just wanted to say is we all want the perfect predictor and all I'm saying is before we claim something is the perfect predictor, it should be.
1:27:8.765 --> 1:27:32.255
Kimberly Van Zee
The transparently reported in terms of area under the Roc curve, the C statistic, all of those things, and if you notice that is never done for either the Oncotype DCIS for or Prelude RT, they never report that for Oncotype DCIS score, I have pretty good evidence that it's poor and that's why they haven't done it.
1:27:32.745 --> 1:27:44.235
Kimberly Van Zee
I also know in a head-to-head comparison in the Kaiser data, per Troy Brenner, the Nomogram did better than Prelude RT in predicting risk of recurrence.
1:27:44.405 --> 1:27:58.245
Kimberly Van Zee
So all I'm asking for is a publication of actual apples to apples comparisons before we commit to these things that are they're holding out as a pie in the sky prize, and I'm all for it if it's proven.
1:27:51.435 --> 1:27:51.665
John Williams
Never.
1:27:58.305 --> 1:28:0.315
Kimberly Van Zee
But I don't think it's proven.
1:28:0.325 --> 1:28:1.675
Kimberly Van Zee
I know it's not proven.
1:28:0.745 --> 1:28:1.85
John Williams
What?
1:28:1.605 --> 1:28:6.175
John Williams
What is the standard of care for a luminal a cancer with its node negative?
1:28:1.685 --> 1:28:2.665
Kimberly Van Zee
There's no evidence.
1:28:6.465 --> 1:28:8.255
John Williams
What genomic assay is there?
1:28:6.825 --> 1:28:7.695
Kimberly Van Zee
Now I'm talking to you.
1:28:7.825 --> 1:28:9.135
Kimberly Van Zee
I'm talking about DCIS.
1:28:9.65 --> 1:28:14.315
John Williams
I understand, but it is the standard of care, and you just criticized it that it doesn't have the data.
1:28:9.145 --> 1:28:10.145
Kimberly Van Zee
I'm talking about DSS.
1:28:14.445 --> 1:28:16.425
John Williams
So it has ridden to here.
1:28:14.955 --> 1:28:15.985
Kimberly Van Zee
No, no, no.
1:28:16.35 --> 1:28:22.705
Kimberly Van Zee
Oncotype DCIS score I said Oncotype DCIS score not Oncotype DX for invasive cancer.
1:28:21.745 --> 1:28:22.155
John Williams
Thank you.
1:28:22.605 --> 1:28:23.365
John Williams
OK, sorry.
1:28:22.945 --> 1:28:44.435
Kimberly Van Zee
No, I'm we're talking DCIS Card, pure DCIS and so Doctor Bien-Willner, I would just Advocate that before people adopt some new biosignature that there has to be a publication of, you know, the area under the RRC curve, the calibration, the actual predictive ability of that tool before it's adopted.
1:28:26.205 --> 1:28:26.965
Atif Khan
To go.
1:28:26.315 --> 1:28:26.875
John Williams
Thanks for Clarifying.
1:28:44.965 --> 1:29:10.305
Kimberly Van Zee
When you have other things that are free of charge that have been published and are predictive, and the nomogram, even though it's not maybe widely used by some, it has been validated and at least five different institutions around the world and with an AUC similar to you know, again, I've never seen it for Prelude, RT, but in I you see better than the Oncotype DX for invasive cancer actually.
1:29:10.315 --> 1:29:11.855
Kimberly Van Zee
And the only publication I've seen of that.
1:29:12.935 --> 1:29:22.545
Gabriel Bien-Willner
Can I ask a follow up doctor Vanzee, you mentioned that this has been validated in in five institutions.
1:29:21.875 --> 1:29:23.905
Kimberly Van Zee
In about 5, I think it's about five.
1:29:23.975 --> 1:29:25.25
Kimberly Van Zee
I can send you the papers.
1:29:24.505 --> 1:29:26.305
Gabriel Bien-Willner
Are these OK?
1:29:26.315 --> 1:29:28.195
Gabriel Bien-Willner
So those are published validations.
1:29:27.935 --> 1:29:28.645
Kimberly Van Zee
Yeah.
1:29:28.715 --> 1:29:31.885
Kimberly Van Zee
Yep, one was the Harvard Group.
1:29:29.255 --> 1:29:29.635
Gabriel Bien-Willner
OK.
1:29:29.645 --> 1:29:30.15
Gabriel Bien-Willner
Thank you.
1:29:31.995 --> 1:29:34.165
Kimberly Van Zee
Laura Collins was the first author.
1:29:35.75 --> 1:29:39.535
Kimberly Van Zee
One was in Belgium; one was in Holland.
1:29:41.375 --> 1:29:43.155
Kimberly Van Zee
You know, they're just around.
1:29:43.675 --> 1:29:44.975
Atif Khan
I think the, you know just.
1:29:43.945 --> 1:29:50.855
John Williams
There's almost a consensus in our in our group though, that the data is strong enough and I totally validate.
1:29:50.865 --> 1:29:51.295
John Williams
Agree.
1:29:51.685 --> 1:29:58.935
John Williams
You know, value your opinion, but I would also take the consensus of it and we can't go back in time.
1:29:58.945 --> 1:30:2.615
John Williams
I understand we love to have perfect data and satisfy you.
1:30:2.665 --> 1:30:7.775
John Williams
It's already satisfied, shall we say four or five or six of of of us otherwise.
1:30:6.585 --> 1:30:13.325
Kimberly Van Zee
Well but, but I would argue we need a statistician to interpret the data somehow, because you guys are getting fooled.
1:30:7.905 --> 1:30:9.495
John Williams
But one thing is is.
1:30:11.925 --> 1:30:33.755
John Williams
The answer the question for you, it's already answered the question for many more and understanding we can go back in time and also we also can't withhold likely fantastic data which I it may not satisfy you from patients for the next five years until some study that takes 10 years to do which is not coming.
1:30:16.85 --> 1:30:18.525
Atif Khan
Stats reviews for those papers came, but you know.
1:30:33.495 --> 1:30:33.925
Kimberly Van Zee
Yeah.
1:30:34.145 --> 1:30:36.5
Atif Khan
If I may, if I may make a point here.
1:30:34.235 --> 1:30:35.385
Kimberly Van Zee
Yeah, take the same.
1:30:35.455 --> 1:30:41.445
Kimberly Van Zee
Take the same population and compare the two which was done but not published because it showed.
1:30:41.755 --> 1:30:44.315
Kimberly Van Zee
According to Troy Bremmer, the the the Nomogram was better.
1:30:46.275 --> 1:30:47.935
Atif Khan
I think ergo my earlier point.
1:30:47.945 --> 1:30:54.515
Atif Khan
You know, even if you had the perfect asset, it would, it would be problematized to try to, like, convince everyone that it's actually the perfect use.
1:30:54.845 --> 1:31:7.245
Atif Khan
Like in that hypothetical construct, but I think, but I think what I would say is that the answer the question, both the Van Nuys and also the nomogram, you know it was the that they were the state of the art.
1:30:56.215 --> 1:30:57.185
Kimberly Van Zee
That's why you need data.
1:31:7.255 --> 1:31:9.255
Atif Khan
You know, and they're like in that period of time.
1:31:9.265 --> 1:31:11.585
Atif Khan
And they were, they added utility to the practice.
1:31:11.595 --> 1:31:12.805
Atif Khan
And there's nothing wrong with.
1:31:12.815 --> 1:31:14.245
Atif Khan
You know how they were generated?
1:31:14.615 --> 1:31:46.15
Atif Khan
One of the one of the caveats to both to that process though, is that when coming out of a single institution, when you run that kind of discovery and then validation and the data set, but partially some of the patients who receive radiation for what have you reason were sort of removed from that from the source data that the nomogram is then meaning that the patients meaning that the patients who the.
1:31:41.245 --> 1:31:41.475
Kimberly Van Zee
No.
1:31:43.465 --> 1:31:43.685
Kimberly Van Zee
No.
1:31:45.735 --> 1:31:46.5
Alastair Thompson
Either.
1:31:47.575 --> 1:31:47.915
Kimberly Van Zee
Go ahead.
1:31:48.985 --> 1:32:0.265
Atif Khan
Meaning that there is it's there's some bias in how patients are being allocated to radiation that are kind of within that are kind of in you know in those datasets that's cannot not be completely accounted for, yeah.
1:31:58.725 --> 1:32:1.675
Kimberly Van Zee
Of course, of no, of course.
1:32:1.685 --> 1:32:6.345
Kimberly Van Zee
And that's true for all these data sets for Prelude, RT as well, they're all selected.
1:32:6.355 --> 1:32:7.185
Kimberly Van Zee
Who got radiation?
1:32:7.195 --> 1:32:9.745
Kimberly Van Zee
Who didn't get radiation except the Swedish Study?
1:32:8.845 --> 1:32:9.595
Atif Khan
Except this week.
1:32:9.805 --> 1:32:11.305
Atif Khan
Except the sweet yeah, so.
1:32:10.305 --> 1:32:10.695
Kimberly Van Zee
Right.
1:32:10.875 --> 1:32:15.65
Kimberly Van Zee
But there was no statistically significant difference in prediction or prognosis in that study.
1:32:19.245 --> 1:32:19.535
Gabriel Bien-Willner
Thank.
1:32:19.545 --> 1:32:21.225
Gabriel Bien-Willner
Thank you all. Yeah.
1:32:19.665 --> 1:32:22.605
John Williams
Hey, Gabriel, where are we with the questions?
1:32:22.695 --> 1:32:23.875
John Williams
I was just gonna come back to you.
1:32:23.615 --> 1:32:31.285
Gabriel Bien-Willner
We're about halfway there, but I think as now we're gonna start drilling down into things that are already been hit multiple times.
1:32:31.915 --> 1:32:44.45
Gabriel Bien-Willner
So I'm going to to probably go to some of these relatively quickly and I think you'll see some of the questions we'll try to drill down and and sort of hopefully, right.
1:32:44.525 --> 1:32:44.945
Gabriel Bien-Willner
Uh.
1:32:45.365 --> 1:32:56.105
Gabriel Bien-Willner
Pigeonhole you into making it a very explicit, uh, uh comment that we're looking for to try to drive how we should be looking at some of this evidence.
1:32:57.115 --> 1:33:4.865
Gabriel Bien-Willner
So let me so the next question is, we're on #6 out of 11 or 12 uh and the last one is just what did I miss?
1:33:5.675 --> 1:33:6.475
Gabriel Bien-Willner
Question 6.
1:33:6.825 --> 1:33:19.355
Gabriel Bien-Willner
Umm, is there sufficient clinical evidence supporting the use of biomarkers for determining what Medicare patients would not benefit from radiation therapy and should forgo its use?
1:33:20.145 --> 1:33:28.765
Gabriel Bien-Willner
Specifically, BCS only treatment I know this has been 90% of the discussion so far, but if anybody wants to comment further on this, please do so.
1:33:29.395 --> 1:33:32.155
John Williams
Maybe a yes or no answer across the board might be helpful.
1:33:32.625 --> 1:33:40.395
Eileen P. Connolly
Well, the one thing I wanted to point out, Medicare is not only elderly if social Medicaid and that's like 70% of my patients.
1:33:40.405 --> 1:33:42.575
Eileen P. Connolly
So it's it is also affecting younger women.
1:33:42.585 --> 1:33:44.665
Eileen P. Connolly
So just in case it just to be there.
1:33:43.685 --> 1:33:47.495
Gabriel Bien-Willner
So let me let me correct that, that that is actually not the case.
1:33:47.745 --> 1:33:48.825
Gabriel Bien-Willner
NOT while.
1:33:48.835 --> 1:33:59.395
Gabriel Bien-Willner
While Medicaid may fit into some structure the the the contractors writing policy would not be, would not reflect the Medicaid population.
1:33:59.665 --> 1:34:5.125
Gabriel Bien-Willner
It would reflect only really Part B services under Medicare, which will not include Medicaid.
1:34:5.985 --> 1:34:8.275
Eileen P. Connolly
And then how does it affect private insurance?
1:34:8.425 --> 1:34:10.975
Eileen P. Connolly
The decisions you make just out of curious, I mean like.
1:34:10.505 --> 1:34:10.975
Gabriel Bien-Willner
He does.
1:34:12.55 --> 1:34:14.135
Gabriel Bien-Willner
Directly speaking, it doesn't at all.
1:34:14.995 --> 1:34:18.845
Gabriel Bien-Willner
Indirectly speaking, it may because they may take our guide.
1:34:15.215 --> 1:34:15.535
Eileen P. Connolly
But they.
1:34:18.855 --> 1:34:25.575
Gabriel Bien-Willner
Our policy as guidance for their Policy, it may they could copy paste our Policy, cut the cost them nothing.
1:34:25.585 --> 1:34:28.635
Gabriel Bien-Willner
To do that, they could disagree with our policy and throw it in the trash.
1:34:32.775 --> 1:34:35.5
John Williams
But in reality it does drive a lot of it.
1:34:35.15 --> 1:34:37.875
John Williams
It just secondarily, but that's not the point of this call, but.
1:34:37.395 --> 1:34:50.955
Gabriel Bien-Willner
And let me let me actually add one more thing that I that maybe should be explicitly stated, which is if you have uh, if you have a Medicare Advantage.
1:34:52.685 --> 1:34:58.835
Gabriel Bien-Willner
Technically, that's still commercial insurance, but they still have to abide by the policies of Medicare.
1:34:58.845 --> 1:35:1.5
Gabriel Bien-Willner
So it would affect Medicare Advantage as well.
1:35:3.345 --> 1:35:4.945
Atif Khan
I'll take a stab at answering you.
1:35:3.575 --> 1:35:4.5
John Williams
Gave me.
1:35:4.135 --> 1:35:6.305
John Williams
Wanna yes or no to the question you asked?
1:35:6.355 --> 1:35:8.435
John Williams
How about that you asked?
1:35:8.445 --> 1:35:11.545
John Williams
Basically, are biomarkers important in playing a role?
1:35:11.555 --> 1:35:13.25
John Williams
Should they be playing a role?
1:35:13.35 --> 1:35:14.775
John Williams
Is that correct in this decision?
1:35:14.545 --> 1:35:17.655
Gabriel Bien-Willner
I said is there sufficient clinical evidence?
1:35:17.865 --> 1:35:19.255
Gabriel Bien-Willner
Not what is your opinion?
1:35:19.295 --> 1:35:20.635
Gabriel Bien-Willner
I said, what of?
1:35:20.645 --> 1:35:32.115
Gabriel Bien-Willner
Whether you think they should be used, but is your hope is what is your opinion whether there's sufficient clinical evidence supporting the use of biomarker testing for determining patients?
1:35:32.125 --> 1:35:36.305
Gabriel Bien-Willner
Who should basically forego RT and get BCS only treatment?
1:35:37.15 --> 1:35:37.625
John Williams
Yes.
1:35:37.815 --> 1:35:38.965
John Williams
How about everybody answer?
1:35:38.975 --> 1:35:39.415
John Williams
Yes or no.
1:35:40.945 --> 1:35:41.105
Alastair Thompson
Yes.
1:35:43.145 --> 1:35:43.535
John Williams
A reef.
1:35:43.585 --> 1:35:46.185
Eileen P. Connolly
Yes, I say yes, I'm using it.
1:35:44.605 --> 1:35:45.985
Brian J. Czerniecki
Yep, yes.
1:35:46.695 --> 1:35:48.815
John Williams
And uh Kim?
1:35:47.385 --> 1:35:47.485
Anne Peled
Yes.
1:35:49.525 --> 1:35:49.765
Kimberly Van Zee
No.
1:35:51.425 --> 1:35:52.685
John Williams
I think that gives you your answer.
1:35:53.725 --> 1:35:56.75
Atif Khan
Wait, I didn't say anything, but yeah.
1:35:54.875 --> 1:35:56.295
Eileen P. Connolly,
Yeah, it was gonna be a Team quarter.
1:35:55.725 --> 1:35:57.355
John Williams
Oh, I thought you OK.
1:35:55.945 --> 1:35:56.245
Kimberly Van Zee
Actually.
1:35:58.265 --> 1:35:59.395
Atif Khan
I would say yes.
1:35:59.405 --> 1:36:2.905
Atif Khan
Asterisks, you know, with an asterisk, but yeah.
1:36:0.905 --> 1:36:1.65
Eileen P. Connolly
Yeah.
1:36:1.485 --> 1:36:1.625
Alastair Thompson
Yeah.
1:36:4.225 --> 1:36:4.425
Alastair Thompson
Yeah.
1:36:4.375 --> 1:36:7.75
Gabriel Bien-Willner
Can you define that asterisk while we're here?
1:36:6.75 --> 1:36:7.405
Atif Khan
Yeah, it it it's.
1:36:7.555 --> 1:36:8.25
Atif Khan
Sure.
1:36:8.35 --> 1:36:10.395
Atif Khan
I I think the asterisk is that it's in the absence of.
1:36:12.625 --> 1:36:12.905
Atif Khan
You know.
1:36:15.275 --> 1:36:21.855
Atif Khan
We have an evidence gap, but we have a clinical need and an evidence we should say evidence that that's kind of a different term.
1:36:15.765 --> 1:36:15.895
Alastair Thompson
Yeah.
1:36:21.915 --> 1:36:24.145
Atif Khan
We have a clinic, we have an unmet clinical need.
1:36:24.155 --> 1:36:25.215
Atif Khan
That's tremendous.
1:36:25.5 --> 1:36:25.245
Eileen P. Connolly
Yes.
1:36:25.595 --> 1:36:26.995
Atif Khan
And this is sort of the.
1:36:27.675 --> 1:36:33.905
Atif Khan
I my reading of this data, the bio signature payload X is not not archetypes.
1:36:33.915 --> 1:36:49.595
Atif Khan
Just because your question is neutral, but that specific assay seems to be very promising and you know the evidentiary standard for you know, using a clinically, has it been met the little bit in the eye of the beholder.
1:36:48.275 --> 1:36:48.395
Kimberly Van Zee
Yeah.
1:36:50.75 --> 1:36:51.345
Atif Khan
My answer is yes.
1:36:51.355 --> 1:36:55.855
Atif Khan
Asterisks because I think there's it's, it's an improvement over what currently exists in the in the science.
1:36:56.815 --> 1:37:14.765
Alastair Thompson
That is probably the evidence at the moment, rather than 1A, and I think from the randomized trial, NRG will be running and and by the way, Kim, it's actually one of the Co leads of that is our friend you were quoting earlier as a doubter of the test.
1:36:56.925 --> 1:36:57.345
John Williams
The level.
1:36:57.85 --> 1:36:58.705
Kimberly Van Zee
But it's not it.
1:37:4.695 --> 1:37:4.915
Eileen P. Connolly
Yes.
1:37:14.865 --> 1:37:19.375
Alastair Thompson
So Wendy Woodward will be Co leading that trial through NRG.
1:37:17.645 --> 1:37:20.665
Kimberly Van Zee
Yeah, yeah, she.
1:37:19.785 --> 1:37:22.725
Alastair Thompson
That will give us definitive 1A evidence in about a decade.
1:37:23.315 --> 1:37:32.345
Kimberly Van Zee
Yeah, she read the paper very, very carefully and noted the weaknesses, which, and that's just my my concern.
1:37:23.725 --> 1:37:23.845
Eileen P. Connolly
Yeah.
1:37:32.355 --> 1:37:41.175
Kimberly Van Zee
There is a great unmet need and I feel like everyone wants to have that need met and they're very good at marketing.
1:37:41.185 --> 1:37:54.455
Kimberly Van Zee
They're very good at presenting their data, but there's no statistically significant difference in hazard ratios of risk reduction by radiation in their low-risk group and their elevated risk group or their elevated risk group and their residual risk group.
1:37:54.505 --> 1:37:58.965
Kimberly Van Zee
There is no statistically significant difference, so that's the problem.
1:37:59.415 --> 1:38:0.805
Atif Khan
You mean within? Without radiation?
1:38:0.815 --> 1:38:3.555
Atif Khan
There's a certificate difference, or no there is there is.
1:38:1.355 --> 1:38:2.25
Kimberly Van Zee
Yeah.
1:38:2.315 --> 1:38:2.705
Kimberly Van Zee
No.
1:38:2.775 --> 1:38:6.45
Kimberly Van Zee
The hazard ratios are no, no, no.
1:38:3.585 --> 1:38:4.765
Eileen P. Connolly
No, there is no there.
1:38:4.775 --> 1:38:5.355
Eileen P. Connolly
Definitely.
1:38:6.5 --> 1:38:6.425
Alastair Thompson
Alright.
1:38:6.55 --> 1:38:15.295
Kimberly Van Zee
There hazard ratios are numerically different, but the hazard ratios are not statistically significantly different from one another.
1:38:16.675 --> 1:38:18.345
John Williams
Gay, why don't we move on to the next one?
1:38:18.355 --> 1:38:27.895
John Williams
I would also end this by saying that I think the level evidence meets the clinical need for DCIS and DCA's complicated, but let's that would be my last input.
1:38:27.935 --> 1:38:30.235
John Williams
What would that next question be serve you?
1:38:28.685 --> 1:38:29.265
Gabriel Bien-Willner
Thank you.
1:38:30.385 --> 1:38:31.675
Gabriel Bien-Willner
Thank you, Doctor Williams.
1:38:31.685 --> 1:38:42.925
Gabriel Bien-Willner
I appreciate all your answers to that and I I again I wanna specify that the answer was sufficient clinical evidence and not really referencing the clinical need.
1:38:42.935 --> 1:38:58.435
Gabriel Bien-Willner
But I do agree that those are things are difficult to separate because different different levels of evidence needed will be altered by the the amount of clinical need or absence of available alternatives.
1:38:59.375 --> 1:39:3.895
Gabriel Bien-Willner
The second question is what are the differences between clinical only risk stratification?
1:39:3.905 --> 1:39:8.595
Gabriel Bien-Willner
Move down and biomarker-based ones in terms of accurate risk assessment.
1:39:9.725 --> 1:39:13.275
Gabriel Bien-Willner
Uh, when would you consider one or the other?
1:39:13.285 --> 1:39:14.395
Gabriel Bien-Willner
Although that second.
1:39:14.785 --> 1:39:16.195
Gabriel Bien-Willner
Yeah, I'll just stop there.
1:39:16.305 --> 1:39:29.245
Gabriel Bien-Willner
It seems like a lot of you don't use the clinical only and it's not really clear to me exactly why that is and anymore information on that would be beneficial to us.
1:39:30.95 --> 1:39:31.395
Gabriel Bien-Willner
Umm, is there?
1:39:31.95 --> 1:39:32.805
Anne Peled
I think oh, sorry.
1:39:32.235 --> 1:39:32.515
Gabriel Bien-Willner
Go ahead.
1:39:32.815 --> 1:39:32.935
Anne Peled
Good.
1:39:34.115 --> 1:39:43.205
Anne Peled
Now it's just gonna say I think for me, when you look at the data and see how many of both clinical low risk and clinical high-risk patients are being reclassified into different groups, right?
1:39:34.315 --> 1:39:34.725
Gabriel Bien-Willner
No, please.
1:39:43.215 --> 1:39:49.485
Anne Peled
Essentially, we're routinely overtreating or under treating people using clinical pathologic features alone.
1:39:49.555 --> 1:39:59.555
Anne Peled
So for me, I think the ability to give people that data and really classify them appropriately does mean that I think that's the best choice for patients rather than using clinical pathological features alone.
1:40:0.475 --> 1:40:14.835
Kimberly Van Zee
But that's assuming that's assuming though that the test is correct in in the Oncotype, which I know is a different test, but Oncotype, when I actually had a bunch of Oncotype values and DC's when you looked at their reclassification, it was incorrect.
1:40:0.545 --> 1:40:0.995
Atif Khan
Yeah, our.
1:40:0.595 --> 1:40:0.755
Alastair Thompson
Yeah.
1:40:15.925 --> 1:40:16.555
Kimberly Van Zee
So it was.
1:40:16.215 --> 1:40:18.25
Anne Peled
But you just said that's a different task.
1:40:16.565 --> 1:40:17.405
Kimberly Van Zee
It was reclassified.
1:40:18.35 --> 1:40:20.595
Anne Peled
So I I think we all do believe in the prelude data.
1:40:18.515 --> 1:40:19.915
Kimberly Van Zee
No, I know I don't have it.
1:40:20.635 --> 1:40:22.265
Anne Peled
So that's what we're talking about today.
1:40:22.275 --> 1:40:26.735
Anne Peled
And I think what those data, the reclassification based on the studies is correct.
1:40:22.845 --> 1:40:23.5
Kimberly Van Zee
No.
1:40:26.745 --> 1:40:30.935
Anne Peled
So I think that's why we're using that in this conversation and not on the list.
1:40:30.485 --> 1:40:30.765
Kimberly Van Zee
Well.
1:40:30.885 --> 1:40:35.935
Atif Khan
I think the the prognostic implications, the reclassification are clear, right?
1:40:36.845 --> 1:40:43.775
Atif Khan
Meaning that you can show different risks of IBR and I think also invasive recurrence by the reclassification.
1:40:43.975 --> 1:40:44.355
Alastair Thompson
Yeah.
1:40:44.105 --> 1:40:56.415
Atif Khan
So leaving aside the predictive, you know thing of it, Kim, I think you can say and in our conversation has been focused exclusively on the low-risk patients getting reclassified due to gain treatment there.
1:40:44.625 --> 1:40:44.785
Kimberly Van Zee
But.
1:40:54.345 --> 1:40:54.465
Eileen P. Connolly
Yeah.
1:40:56.485 --> 1:41:0.955
Atif Khan
But equally compelling is I think and I'm grateful to add to bring this up.
1:41:0.965 --> 1:41:2.515
Atif Khan
And we haven't because we didn't talk about this.
1:41:2.525 --> 1:41:18.975
Atif Khan
Is that the highest ones are also getting reclassified and it's kind of interesting when you look at the in the net kind of like the proportion of patients who are low versus high, it's almost sort of the same as the clean path, but they're actually very it's very different because they've been reclassified from the two groups.
1:41:19.825 --> 1:41:48.815
Kimberly Van Zee
Well, one of the things that they include in their prelude RT score, R age, size, margin status and palpability they include those in that score and it's not clear what proportion of their predictability is from those items versus from the biosignature in Oncotype DCIS, where I can tell you 97% of it is from the clinical factors that are in there, not from the DCIS score in the recent rajkovich paper.
1:41:19.975 --> 1:41:20.155
Alastair Thompson
Yeah.
1:41:20.175 --> 1:41:20.415
Eileen P. Connolly
Right.
1:41:28.235 --> 1:41:28.375
Atif Khan
Yeah.
1:41:29.205 --> 1:41:30.5
Eileen P. Connolly
Yeah, but when they.
1:41:49.365 --> 1:41:58.275
Atif Khan
They don't report that, but the the rates of like reassortment and reclassification and and these patients who are otherwise being cleaned path sorted is pretty significant.
1:41:49.635 --> 1:41:49.935
Eileen P. Connolly
Well.
1:41:57.825 --> 1:41:59.85
Eileen P. Connolly
Is significant, yeah.
1:41:58.285 --> 1:42:2.845
Atif Khan
So you kind of have to believe that, you know, there's a driver there that's unique.
1:41:59.225 --> 1:41:59.465
Kimberly Van Zee
Right.
1:42:1.45 --> 1:42:20.705
Kimberly Van Zee
But it it also I know but a lot of their when they developed it they they developed it in the population in which they're reporting for large part and only in the recent Australian and Kaiser and the Kaiser goes way back.
1:42:1.255 --> 1:42:1.535
Eileen P Connolly
OK.
1:42:2.765 --> 1:42:5.425
Eileen P. Connolly
Yeah, they tell you that they give you like a.
1:42:20.715 --> 1:42:40.565
Kimberly Van Zee
So I know they were aware of the Kaiser data long years decade ago, but it's not clear what is actually a true prospective validation versus its they've all been added the RRT based on some component of these data that is not clear and they didn't report which is unfortunate.
1:42:21.115 --> 1:42:21.355
Atif Khan
Mm-hmm.
1:42:24.515 --> 1:42:24.875
Atif Khan
Umm.
1:42:38.455 --> 1:42:52.445
John Williams
You know, one of the questions that come up in the chat is can you estimate what percentage of patients would avoid radiation therapy using preload, prelude, RT and that general answer is about 40 to 50%.
1:42:52.835 --> 1:43:0.545
John Williams
It is a really significant number of people that we otherwise would most likely be recommended radiation and we pull out of that account, avoid.
1:43:0.775 --> 1:43:2.225
John Williams
We've talked about radiation.
1:43:2.695 --> 1:43:4.145
John Williams
I'm a breast cancer surgeon.
1:43:4.215 --> 1:43:12.735
John Williams
Probably as long as just about anyone here and the ultimate long-term effects of radiation are significant. Period.
1:43:12.605 --> 1:43:12.845
Kimberly Van Zee
I.
1:43:12.845 --> 1:43:13.645
John Williams
I see it.
1:43:13.745 --> 1:43:15.185
John Williams
The patients don't know it up front.
1:43:15.195 --> 1:43:16.765
John Williams
We gloss over cause it's complicated.
1:43:16.775 --> 1:43:25.875
John Williams
Some people get it, but the IT is a real significant long-term life changing, if not life somewhat altering problem.
1:43:25.885 --> 1:43:29.795
John Williams
So I'm what I'm sharing is those that we can avoid radiation in.
1:43:30.65 --> 1:43:38.135
John Williams
We've done not only a good thing, we've done an incredible service and finding those that can avoid it, that is sophisticated care.
1:43:36.695 --> 1:43:36.855
Kimberly Van Zee
Yeah.
1:43:38.145 --> 1:43:43.235
John Williams
The same outcome with less intervention and side effects, and that's where it kind of go back.
1:43:43.245 --> 1:43:45.285
John Williams
So I thought that question was helpful.
1:43:45.355 --> 1:43:47.225
John Williams
Gabe, is there another question you wanna move on?
1:43:46.285 --> 1:43:57.75
Kimberly Van Zee
It and to follow up on that in using the nomogram, if you take people that take endocrine therapy, we had 80% of our patients have a under 10% risk of recurrence.
1:43:47.235 --> 1:43:48.45
John Williams
We're running out of time.
1:43:57.145 --> 1:44:7.635
Kimberly Van Zee
This is in the paper I did comparing Oncotype DCIS for with the nomogram, but it was 80% of those that take endocrine therapy would have an under 10% risk.
1:44:7.705 --> 1:44:8.875
Kimberly Van Zee
These are in women over 50.
1:44:7.855 --> 1:44:13.955
Anne Peled
But we know that people still barely complete their under therapy for, I mean that we can't rely on that to determine the score.
1:44:9.575 --> 1:44:10.145
Brian J Czerniecki
But but.
1:44:10.155 --> 1:44:11.185
Brian J. Czerniecki
But can you get?
1:44:11.235 --> 1:44:14.265
Brian J. Czerniecki
Can you guarantee someone it?
1:44:14.315 --> 1:44:20.55
Brian J. Czerniecki
Can you guarantee someone's at the beginning you're gonna predict is gonna continue on endocrine therapy from the end?
1:44:18.65 --> 1:44:18.525
Anne Peled
Exactly.
1:44:19.865 --> 1:44:21.255
Kimberly Van Zee
No, no.
1:44:20.65 --> 1:44:24.255
Brian J. Czerniecki
I haven't been able to do that, so I was just curious to how that happens.
1:44:24.915 --> 1:44:26.795
Kimberly Van Zee
Well, but I I mean, you can't.
1:44:26.805 --> 1:44:35.885
Kimberly Van Zee
You're right, but in the Prelude RT development population and in the Oncotype population, a significant proportion of people took endocrine therapy.
1:44:35.955 --> 1:44:37.5
Eileen P. Connolly
No, they didn't.
1:44:35.975 --> 1:44:36.705
Kimberly Van Zee
So we don't know.
1:44:37.455 --> 1:44:41.655
Eileen P Connolly
No, actually a majority did not actually in their cohorts did not.
1:44:39.465 --> 1:44:40.495
Kimberly Van Zee
A majority didn't.
1:44:40.505 --> 1:44:41.675
Kimberly Van Zee
I I didn't say a majority.
1:44:41.685 --> 1:44:44.695
Kimberly Van Zee
I said a significant number did, though I don't.
1:44:44.175 --> 1:44:52.105
Alastair Thompson
And in some of those in some of those studies, for example, the Australian subpopulation, they do not use tamoxifen, they do not use endocrine therapy.
1:44:44.555 --> 1:44:44.865
Eileen P. Connolly
I'm.
1:44:44.705 --> 1:44:46.405
Kimberly Van Zee
It was like 20 or 30%.
1:44:50.395 --> 1:44:50.825
Brian J. Czerniecki
For that.
1:44:52.115 --> 1:44:54.105
Alastair Thompson
And yet it still seems to bear out.
1:44:52.555 --> 1:44:55.605
Kimberly Van Zee
It in the Kaiser.
1:44:54.475 --> 1:44:59.165
Alastair Thompson
So I think that tamoxifen, the tamoxifen question was the.
1:44:56.325 --> 1:44:58.35
Eileen P. Connolly
It was only 30% I believe.
1:44:58.475 --> 1:45:1.5
Kimberly Van Zee
Yeah, 30%, but that's a significant minority.
1:45:1.15 --> 1:45:3.395
Kimberly Van Zee
So that's another factor that.
1:45:2.835 --> 1:45:13.935
Eileen P. Connolly
It's not gonna give you a 10 Year 5% in the low risk, which is I mean essentially they're showing 5% at 10 years with the low-risk cohort and that's better than what you would get with just the clinical pathologic.
1:45:13.945 --> 1:45:21.725
Eileen P. Connolly
I mean, that's what they're doing, is they're picking out the lowest risk they are giving you that pretty so I know.
1:45:19.575 --> 1:45:20.5
Gabriel Bien-Willner
Can I?
1:45:20.15 --> 1:45:22.405
Gabriel Bien-Willner
I'd like to just interrupt this conversation.
1:45:22.415 --> 1:45:31.215
Gabriel Bien-Willner
While it's great, I do want, I do believe we're out running risk of not getting through all the questions and I do appreciate the lively discussion has been very entertaining.
1:45:22.735 --> 1:45:22.855
Alastair Thompson
Yeah.
1:45:28.535 --> 1:45:29.35
Alastair Thompson
That's great.
1:45:31.955 --> 1:45:56.285
Gabriel Bien-Willner
Umm, I will move on to question 7, which is it was noted even from the very beginning of this discussion that I think several of you commented that there are subsets of patients based on a number of factors that you would always recommend having radiation therapy or maybe never.
1:45:57.545 --> 1:45:57.985
Gabriel Bien-Willner
Umm.
1:45:58.405 --> 1:46:7.565
Gabriel Bien-Willner
And what I wanted to do is to find if to see if we could define he population or subpopulation of patients.
1:46:8.895 --> 1:46:20.745
Gabriel Bien-Willner
Umm where in ah a group of patients are most likely to benefit from from these kinds of services.
1:46:20.755 --> 1:46:23.845
Gabriel Bien-Willner
So the language was of the of the specific question.
1:46:23.855 --> 1:46:24.505
Gabriel Bien-Willner
What are the?
1:46:24.735 --> 1:46:25.425
Gabriel Bien-Willner
No, I'm sorry.
1:46:25.435 --> 1:46:28.305
Gabriel Bien-Willner
I meant question eight.
1:46:29.255 --> 1:46:29.615
Gabriel Bien-Willner
Uh.
1:46:29.875 --> 1:46:39.185
Gabriel Bien-Willner
In what patient population specifically have demonstrated improved outcomes from these Services, improved outcomes here can mean avoiding unnecessary interventions.
1:46:39.335 --> 1:46:46.285
Gabriel Bien-Willner
Is there any evidence that biomarker testing improves risk stratification or outcomes in clinical substrate fication methods?
1:46:48.205 --> 1:46:56.225
Gabriel Bien-Willner
Sorry, I really wanted to focus on Support on specific populations like where it's clear that those do those benefit more than the general population.
1:46:57.355 --> 1:46:57.745
John Williams
Maybe.
1:46:57.755 --> 1:47:10.255
John Williams
Anne, why don't we ask you, just since you do this in practice every day out in California and I'm on the East Coast, but when you see patients in that top level, what factors are are making you say you need radiation?
1:47:10.265 --> 1:47:11.985
John Williams
You really be crazy not to do it.
1:47:12.315 --> 1:47:16.345
John Williams
Would it be a biosignature first, followed by age, followed by grade?
1:47:16.355 --> 1:47:16.855
John Williams
What would it be?
1:47:19.85 --> 1:47:28.455
Anne Peled
I mean, I think certainly again in my mind, I think having the biosignature data is incredibly helpful just because of the large proportion of people that get reclassified, as we said on both sides.
1:47:28.465 --> 1:47:44.255
Anne Peled
So that's why for me, I actually rarely am going to tell someone that I 100% can guess or know from their clinical pathologic features alone that they're going to what it can tell them about their actual benefit from radiation is, I will say like we do in general, I think once we get to the extreme ends, right.
1:47:44.265 --> 1:47:55.865
Anne Peled
So if I have very young patients, which I know isn't relevant for this conversation but very young patients where we just don't have enough patience in these trials, that's a situation where I might start thinking that perhaps this test is less helpful.
1:47:56.315 --> 1:48:1.945
Anne Peled
Certainly people with very large areas, if disease where we're starting to have areas of micro invasive cancer.
1:48:1.955 --> 1:48:18.365
Anne Peled
I think again, we run into those and then again on the extreme ends, right, if you have someone who is 95 and is in a situation where we really know that not only is there not gonna be a survival benefit that getting them ten years of decreased recurrence and knowing that isn't going to be particularly helpful.
1:48:18.375 --> 1:48:23.645
Anne Peled
But again, I find for most patients with the data we have that being able to see if they're going to be reclassified as helpful.
1:48:26.95 --> 1:48:28.185
Atif Khan
Can I take a stab and answer the question?
1:48:27.165 --> 1:48:27.325
Gabriel Bien-Willner
Thank.
1:48:28.695 --> 1:48:37.45
Atif Khan
Doctor Bien-Willner, I think if so caveat we don't we currently aren't using this test in any routine way at our institution.
1:48:31.865 --> 1:48:32.305
Gabriel Bien-Willner
Yeah, of course.
1:48:37.455 --> 1:48:43.525
Atif Khan
But if a patient came to me who had completely low risk features, everything was good, right?
1:48:43.535 --> 1:48:47.165
Atif Khan
Low grade, High age, widely negative margin.
1:48:47.175 --> 1:48:51.865
Atif Khan
Everything was perfect, but they happened to come with a report where the bias signature was high.
1:48:52.595 --> 1:48:53.505
Atif Khan
I would treat them.
1:48:53.675 --> 1:48:55.845
Atif Khan
I would not feel comfortable if not treating that patient.
1:48:56.645 --> 1:49:0.715
Atif Khan
I think the flip side of it, and I think the evidentiary standard is, is there for that.
1:49:0.725 --> 1:49:1.575
Atif Khan
I think I can.
1:49:1.725 --> 1:49:19.445
Atif Khan
I can justify that to myself and and, and I think the flip side of it would be if somebody who had a clear indication, you know what we can currently consider sort of a, quote unquote clear indication for radiation, let's say high grade disease, but they're biased signature report that they come to me with in their hand suggests a very low risk.
1:49:19.455 --> 1:49:22.95
Atif Khan
They're in the low risk of the RRT.
1:49:22.705 --> 1:49:26.535
Atif Khan
What I feel comfortable omitting radiotherapy in that I think that's a little bit harder.
1:49:26.545 --> 1:49:27.365
Atif Khan
That's a little trickier.
1:49:27.255 --> 1:49:27.395
Eileen P. Connolly
Yeah.
1:49:27.375 --> 1:49:33.65
Atif Khan
I think I probably would still offer that patient radiation until we have that level one evidence that.
1:49:35.185 --> 1:49:36.665
Atif Khan
That Alistair was referring to earlier.
1:49:37.765 --> 1:49:38.355
Eileen P. Connolly
I agree.
1:49:38.5 --> 1:49:38.635
Kimberly Van Zee
And I think so.
1:49:38.405 --> 1:49:38.845
Eileen P. Connolly
I would.
1:49:38.925 --> 1:49:40.835
Eileen P. Connolly
I would say it does impact.
1:49:40.905 --> 1:49:42.315
Eileen P. Connolly
I might not give them a boost.
1:49:42.465 --> 1:49:46.55
Eileen P. Connolly
Their course is gonna get shorter, so I don't know if that's true for you.
1:49:45.775 --> 1:49:46.795
Atif Khan
Over the high-risk ones?
1:49:46.805 --> 1:49:47.545
Atif Khan
Yeah, that's a good point.
1:49:46.965 --> 1:49:47.275
Eileen P. Connolly
Yeah.
1:49:47.285 --> 1:49:53.615
Eileen P. Connolly
For the high risk, I mean, I I won't boost them, so maybe they'll get a little less toxicity and it's a weak shorter, but I agree.
1:49:47.555 --> 1:49:50.205
Atif Khan
Yeah, yeah, yeah, yeah.
1:49:52.815 --> 1:50:6.665
Kimberly Van Zee
And I think other some other factors are close margin or a very large extent of disease or a younger age or a combination of above all of those would you know make you hesitant to not radiate them.
1:50:6.675 --> 1:50:10.75
Kimberly Van Zee
I think because there's really good data for all those that matter.
1:50:10.715 --> 1:50:11.335
Atif Khan
Yeah, yeah.
1:50:10.995 --> 1:50:14.835
Eileen P. Connolly
Yeah, but I think there is data for, you know, who do we boost right now.
1:50:14.845 --> 1:50:20.925
Eileen P Connolly
I use the boost trial, the Trog 07 Study, and I mean I'm using set criteria.
1:50:20.935 --> 1:50:27.965
Eileen P. Connolly
But if I get a 45-year-old and the only thing that's high risk is their age, if I can avoid the boost that makes, that's something I'm saving her.
1:50:28.255 --> 1:50:30.655
Eileen P. Connolly
So it yeah, I find that helpful.
1:50:28.525 --> 1:50:30.345
Atif Khan
Umm, that's fair, yeah.
1:50:31.775 --> 1:50:32.695
John Williams
A Brian.
1:50:34.255 --> 1:50:59.345
Brian J. Czerniecki
I would say the group that has the biggest gain that I would definitely do radiation is that residual risk type because we're talking about somebody who's around 20% risk of invasive cancer being lowered and those tumors that they're gonna subsequently develop are not chicken feed, those are chemo treated patients.
1:50:42.955 --> 1:50:43.705
Atif Khan
Oh yeah, for sure.
1:50:56.145 --> 1:50:56.325
Atif Khan
Yeah.
1:50:57.25 --> 1:50:57.265
Alastair Thompson
You know.
1:50:57.345 --> 1:50:57.805
Eileen P. Connolly
That's true.
1:50:59.355 --> 1:51:3.925
Brian J. Czerniecki
And to ignore that group is, as physicians, we should be ashamed of ourselves.
1:50:59.515 --> 1:50:59.835
Atif Khan
I mean.
1:51:4.465 --> 1:51:5.305
Eileen P. Connolly
Yeah, I think.
Atif Khan
And Elvin chemist, still skeptical and sort of saying we're all crazy, but I think.
1:51:8.15 --> 1:51:10.375
Atif Khan
I think if the residual risk and then.
1:51:8.515 --> 1:51:23.545
Brian J Czerniecki
Well, I can say having published 5 papers used looking at her two expression in clinical DCIS and that's a pathway off of the path they found and finding invasive cancer associated with those at a much higher rate.
1:51:9.855 --> 1:51:10.25
Kimberly Van Zee
But.
1:51:23.595 --> 1:51:28.855
Brian J. Czerniecki
I gotta believe that that Test is picking up a very high-risk group.
1:51:26.705 --> 1:51:26.855
Kimberly Van Zee
Hi.
1:51:27.765 --> 1:51:29.505
Atif Khan
Those numbers are staggering.
1:51:28.595 --> 1:51:34.615
Kimberly Van Zee
Well, Dr. Czerniecki, I agree, but just test it for her too.
1:51:29.515 --> 1:51:30.905
Atif Khan
I would say that the residual.
1:51:34.685 --> 1:51:39.745
Kimberly Van Zee
So her too high grade, close margin, younger age, all of those are important factors.
1:51:39.395 --> 1:51:43.595
Brian J. Czerniecki
It so you planned that it turns out not to.
1:51:40.765 --> 1:51:42.995
Alastair Thompson
How to test alone this doesn't work.
1:51:43.305 --> 1:51:43.465
John Williams
Yeah.
1:51:43.605 --> 1:51:45.495
Brian J. Czerniecki
And we don't routinely test.
1:51:44.965 --> 1:51:45.425
Alastair Thompson
Doesn't work.
1:51:45.545 --> 1:51:51.995
Brian J. Czerniecki
I don't know how many patients you get coming in your office with her to testing on their DCIS, but it's not even there.
1:51:51.745 --> 1:51:54.545
Eileen P. Connolly
Unfortunately, be 43 didn't meet its primary aim.
1:51:52.135 --> 1:51:54.805
John Williams
Let's not dive into that because we've got other questions.
1:51:54.975 --> 1:51:56.305
John Williams
We got other questions coming.
1:51:56.125 --> 1:51:57.365
Atif Khan
Yeah, we should keep going, yeah.
1:51:56.355 --> 1:51:58.125
John Williams
Alastair, what's your final on this?
1:51:58.15 --> 1:52:5.765
Gabriel Bien-Willner
I think Dr. Williams these will be pretty short and to the point I'd like to really pigeonhole some very specific circumstances here.
1:52:6.595 --> 1:52:7.605
Gabriel Bien-Willner
Question 9.
1:52:7.615 --> 1:52:11.885
Gabriel Bien-Willner
If a biomarker identifies a quote low risk, uh, Group.
1:52:13.235 --> 1:52:23.795
Gabriel Bien-Willner
Uh of 10% I PR that is not statistically associated with RT response and the clinical only feature strategy predicts.
1:52:24.345 --> 1:52:25.275
Gabriel Bien-Willner
Uh, uh.
1:52:25.325 --> 1:52:26.135
Gabriel Bien-Willner
Low risk?
1:52:26.205 --> 1:52:27.515
Gabriel Bien-Willner
Uh, in a low-risk group?
1:52:27.555 --> 1:52:28.975
Gabriel Bien-Willner
Uh, uh.
1:52:29.485 --> 1:52:37.55
Gabriel Bien-Willner
Sorry, I, BTR and now and a low-risk group of 10% without any claims to statistical lack of RT response in that group.
1:52:38.85 --> 1:52:40.805
Gabriel Bien-Willner
Does that carry significance in decision making?
1:52:42.515 --> 1:52:44.215
Gabriel Bien-Willner
If that the memo that doesn't make sense.
1:52:45.315 --> 1:52:45.745
John Williams
Would you?
1:52:45.475 --> 1:52:49.625
Kimberly Van Zee
I it?
1:52:45.755 --> 1:52:48.465
John Williams
It broke up on me and I maybe the others.
1:52:46.445 --> 1:52:47.155
Brian J. Czerniecki
You repeat it.
1:52:48.475 --> 1:52:52.195
John Williams
Would you just summarize it real quick again, I couldn't hear you.
1:52:52.325 --> 1:53:17.565
Gabriel Bien-Willner
If you've got two tests that both one is a molecular test and one is a non-molecular test and they both identify a low-risk group that has a absolute risk of 10% IB TR, but the molecular test also claims that that it is not associated that that low risk group is not associated with RT response.
1:53:19.895 --> 1:53:21.565
Gabriel Bien-Willner
Is there a difference between those two tests?
1:53:23.165 --> 1:53:25.935
Eileen P. Connolly
How much does it reassort the clinical group?
1:53:25.945 --> 1:53:26.545
Eileen P. Connolly
I mean, that's it.
1:53:26.555 --> 1:53:27.255
Eileen P. Connolly
You're not telling me?
1:53:26.905 --> 1:53:28.555
Gabriel Bien-Willner
There, let's assume there is.
1:53:27.965 --> 1:53:28.235
Kimberly Van Zee
Yeah.
1:53:28.245 --> 1:53:28.555
Kimberly Van Zee
Thank you.
1:53:28.605 --> 1:53:32.215
Gabriel Bien-Willner
Let's say that there that they both have 10% IB TR.
1:53:32.225 --> 1:53:33.415
Gabriel Bien-Willner
So it makes no difference.
1:53:33.885 --> 1:53:36.195
Gabriel Bien-Willner
Let's say let's say the molecular Test resorts.
1:53:34.305 --> 1:53:35.235
Eileen P. Connolly
Uh, yeah.
1:53:35.245 --> 1:53:35.955
Eileen P. Connolly
But they're relative.
1:53:35.965 --> 1:53:42.115
Eileen P. Connolly
You're saying that no clinical pathological gets you 10% with what relative reduction in radiation benefit to radiation?
1:53:42.205 --> 1:53:45.95
Eileen P. Connolly
If it takes it to 1%, then that's a different population.
1:53:43.595 --> 1:53:43.915
Kimberly Van Zee
It.
1:53:45.305 --> 1:53:50.365
Eileen P. Connolly
Then if you find something with a molecular marker that says there's no benefit to the radiation, those are two different tests.
1:53:49.645 --> 1:53:53.415
Kimberly Van Zee
5050% he's saying 50%.
1:53:51.255 --> 1:53:51.645
Gabriel Bien-Willner
That's the.
1:53:53.625 --> 1:53:59.275
Kimberly Van Zee
So with the clinical pathologic factors, you know from just all the randomized trials, it'd be 50% risk reduction.
1:53:58.5 --> 1:53:59.965
Eileen P Connolly
Right, 50%, but he's saying.
1:53:59.285 --> 1:54:9.635
Kimberly Van Zee
So he's saying he's saying 10% risk of recurrence and in with one is saying it's reducing it it by zero and the other one it would be a 50% risk reduction.
1:54:3.395 --> 1:54:3.745
John Williams
Let's see.
1:54:3.405 --> 1:54:3.605
Eileen P. Connolly
With.
1:54:9.645 --> 1:54:10.745
Kimberly Van Zee
Would that make a difference to you?
1:54:9.925 --> 1:54:10.175
John Williams
The.
1:54:11.225 --> 1:54:12.545
Eileen P. Connolly
Well, if you're reclassify.
1:54:11.225 --> 1:54:15.305
Gabriel Bien-Willner
But again, the point let me let me let me clarify here.
1:54:16.75 --> 1:54:20.45
Gabriel Bien-Willner
The chances of the patient recurring are exactly the same, but.
1:54:19.535 --> 1:54:20.255
John Williams
Which do you believe?
1:54:19.615 --> 1:54:23.805
Eileen P Connolly
Yeah, but you're not telling me with radiation, the chances of recurrence are exactly the same.
1:54:23.815 --> 1:54:24.565
Eileen P Connolly
Is that what you're saying?
1:54:25.375 --> 1:54:38.55
Gabriel Bien-Willner
Yes, I'm saying that that let me put it how this could work mathematically is that one test is probably overcalling some patients, some patients will respond to their.
1:54:28.625 --> 1:54:29.125
Kimberly Van Zee
Without.
1:54:31.945 --> 1:54:32.605
Eileen P. Connolly
They're not the same.
1:54:38.535 --> 1:54:47.5
Gabriel Bien-Willner
I guess I don't wanna explain that too much, because this certainly could and let me just let's assume they're not the same task.
1:54:40.985 --> 1:54:41.155
John Williams
It's.
1:54:42.115 --> 1:54:43.305
Eileen P. Connolly
But they're not the same.
1:54:44.265 --> 1:54:44.615
Eileen P Connolly
That's why.
1:54:45.425 --> 1:54:45.745
Kimberly Van Zee
OK.
1:54:47.15 --> 1:54:47.705
Gabriel Bien-Willner
No, no, absolutely.
1:54:47.715 --> 1:54:48.745
Gabriel Bien-Willner
They're two different tests.
1:54:49.95 --> 1:54:53.85
Gabriel Bien-Willner
One is a molecular test, and one is a non-molecular test.
1:54:53.575 --> 1:54:58.835
Gabriel Bien-Willner
Both can predict 10% chance I, BTR, and let's say there's infinite data.
1:54:58.875 --> 1:55:1.345
Gabriel Bien-Willner
That suggests that that is an accurate result.
1:55:2.235 --> 1:55:3.265
Eileen P. Connolly
With surgery a lot.
1:55:2.265 --> 1:55:10.235
Gabriel Bien-Willner
But one of the tests, the molecular tests, also shows that patients that are in that low-risk group do not benefit from radiation.
1:55:11.155 --> 1:55:12.365
Gabriel Bien-Willner
Does that matter?
1:55:12.775 --> 1:55:14.705
Gabriel Bien- Willer
Is there a difference between those services?
1:55:14.715 --> 1:55:16.645
Gabriel Bien-Willner
Is 1 service better than another?
1:55:17.55 --> 1:55:22.505
Gabriel Bien-Willner
Despite the fact that the absolute risk of recurrence is actually the same.
1:55:22.825 --> 1:55:24.375
Atif Khan
All right, why don't we go around the room real quick?
1:55:23.285 --> 1:55:23.495
Eileen P. Connolly
No.
1:55:23.335 --> 1:55:23.525
Kimberly Van Zee
With.
1:55:24.385 --> 1:55:25.945
Atif Khan
Let's just because we're out of time, guys.
1:55:24.635 --> 1:55:27.5
John Williams
Just go around, alright. Are we?
1:55:25.955 --> 1:55:26.745
Atif Khan
Yeah, run out of time.
1:55:26.345 --> 1:55:27.165
Eileen P Connolly
Yeah. OK.
1:55:27.25 --> 1:55:36.955
John Williams
What do you think it does biologic outweigh results outweigh clinical path like clinical pathologic or two different tests?
1:55:36.425 --> 1:55:36.585
Alastair Thompson
Yeah.
1:55:36.965 --> 1:55:39.295
John Williams
Which would you choose to treat your patient?
1:55:39.425 --> 1:55:41.65
John Williams
Would you take the biologic result?
1:55:40.955 --> 1:55:42.5
Atif Khan
Alright, I'll go first.
1:55:42.15 --> 1:55:47.515
Atif Khan
I'll go first in that specific context, I don't think the biological test is actually.
1:55:49.185 --> 1:55:52.85
Atif Khan
Valuable, because once you're under 10%.
1:55:53.285 --> 1:55:57.915
Atif Khan
Umm, like we said, DCIS is not life threatening and the salvage rate is like 100%.
1:55:57.925 --> 1:56:12.115
Atif Khan
So it's, you know, like I think if the non-molecular test is also prognostically, you know saying that in a certain group of patients X the risk of IBR is under 10%, All IBR which means the risk of invasive recurrence is even something less than that.
1:56:12.605 --> 1:56:15.245
Atif Khan
I don't know that that. UM.
1:56:14.365 --> 1:56:15.55
John Williams
3 minutes.
1:56:15.65 --> 1:56:16.315
John Williams
We gotta get an answer.
1:56:16.275 --> 1:56:16.625
Atif Khan
Yeah.
1:56:16.585 --> 1:56:19.355
John Williams
We got 3 minutes for this call, OK?
1:56:16.695 --> 1:56:18.255
Atif Khan
So no, my answer is no.
1:56:19.365 --> 1:56:21.585
John Williams
Anne, would you take biologic or the?
1:56:20.535 --> 1:56:21.485
Anne Peled
Uh, yes.
1:56:21.495 --> 1:56:34.405
Anne Peled
And I think the question is asking that if you have one group that allows for classifying people that don't benefit from radiation and the other one doesn't, that in of itself right is additional information beyond just predicting the risk of recurrence.
1:56:34.415 --> 1:56:35.15
Anne Peled
So I would say yes.
1:56:34.775 --> 1:56:34.895
Alastair Thompson
Yeah.
1:56:36.795 --> 1:56:37.425
Eileen P. Connolly
Agree, yes.
1:56:37.115 --> 1:56:37.465
John Williams
OK.
1:56:39.515 --> 1:56:42.965
John Williams
I would take the biologic over the other without a doubt.
1:56:42.975 --> 1:56:43.765
John Williams
That's where we're going.
1:56:43.775 --> 1:56:45.335
John Williams
That's what we're doing in clinical practice.
1:56:45.345 --> 1:56:51.865
John Williams
That's what we're doing with invasive cancer, and we can go back in time otherwise and look from 36,000 feet.
1:56:47.735 --> 1:56:47.935
Alastair Thompson
Yeah.
1:56:51.875 --> 1:56:52.645
John Williams
Kim, what's your type?
1:56:54.725 --> 1:57:10.175
Kimberly Van Zee
Uh, I think with that scenario, the benefit of that additional test is minimal because you have one case where they're both 10% without radiation and one of them with radiation would be 10% and the other one with radiation would be 5%.
1:57:10.525 --> 1:57:15.455
Kimberly Van Zee
And the difference between 5 and 10% is never gonna be shown to be statistically significant in any group.
1:57:15.465 --> 1:57:16.935
Kimberly Van Zee
I mean, it's a very small difference.
1:57:26.15 --> 1:57:26.265
Atif Khan
Yeah.
1:57:26.345 --> 1:57:34.285
Atif Khan
Meaning that the diminishing returns right the at some level of risk that's diminishing returns with the biological asset.
1:57:28.785 --> 1:57:28.905
Kimberly Van Zee
Yes.
1:57:34.295 --> 1:57:40.485
Atif Khan
If they're non-biological assets performing, you know like at the same at the same level but without the predictive.
1:57:38.565 --> 1:57:39.495
John Williams
Alistair, what you're.
1:57:41.35 --> 1:57:50.745
Alastair Thompson
I think the reduction from 10 to 5%, which is 1 in 20 patients for that one out of 20 patients, very significant, I would do the molecular test.
1:57:41.225 --> 1:57:41.685
John Williams
Proud of.
1:57:49.505 --> 1:57:49.625
John Williams
Yeah.
1:57:52.55 --> 1:57:53.215
John Williams
Gabe, what do you got next?
1:57:54.325 --> 1:57:55.15
Atif Khan
Yeah, it's gone.
1:57:55.55 --> 1:57:55.365
Gabriel Bien-Willner
OK.
1:57:55.375 --> 1:58:4.585
Gabriel Bien-Willner
The last quote thank you for All answering that I'm the last question that that has of significance here similar question but different variables.
1:58:5.525 --> 1:58:17.815
Gabriel Bien-Willner
Uh, you have a biomarker test that identifies the lowest population of 10% I, VTR and further identifies a group of patients who are light additionally less likely to have invasive recurrence.
1:58:18.595 --> 1:58:40.955
Gabriel Bien-Willner
How does that information in impact decision making regarding testing and and making PCs versus BCT decisions meaning on, is there an additional consideration and how you additionally consider not just I, BTR, but also knowing whether a predictive model around invasive cancer?
1:58:42.325 --> 1:58:43.245
Atif Khan
OK, I can go first.
1:58:43.255 --> 1:58:43.795
Atif Khan
Yeah, totally.
1:58:43.805 --> 1:58:44.805
Atif Khan
I think that would matter a lot.
1:58:45.695 --> 1:59:12.515
Atif Khan
Umm, I think if the 10% was like 80% invasive like you, let's say this assay was sort of preferentially picking out the the ones that were likely to recur invasive that would be huge and that would influence the thinking just to go back to the prior question in this idea of diminishing returns, if you take the threshold from 10% down to 5% down to 2% down to at some point, everyone in this room would have to say that we don't think the biological assay is actually warranted at some point.
1:59:9.695 --> 1:59:9.835
Eileen P. Connolly
Yeah.
1:59:12.525 --> 1:59:17.945
Atif Khan
So where that threshold is, I don't know, but that's sort of the point I was trying to make.
1:59:19.485 --> 1:59:20.685
Anne Peled
Yep, personally I can.
1:59:20.695 --> 1:59:22.35
Anne Peled
I mean, I would, I would say, certainly yes.
1:59:22.45 --> 1:59:29.365
Anne Peled
I think I continue to feel both my physician and patient hats on that 10% is just too high of a number of recurrences for many people.
1:59:29.375 --> 1:59:43.195
Anne Peled
And I think 5% is a much more appropriate place to land and certainly 15% as we talked about earlier is much too high and no question, right, if you're a patient, everything about patient counseling, being able to tell them what the risk of invasive cancer coming back is is a tremendous ad.
1:59:43.285 --> 1:59:45.565
Anne Peled
And so again, I think that's a definite yes for me.
1:59:45.565 --> 1:59:53.535
Atif Khan
But just to I, sorry, I don't want to perseverate on this, just in the hypothetical that's been framed 1 assay has a predicts a 10% recurrence risk.
1:59:53.545 --> 1:59:57.835
Atif Khan
We don't know what the predictive, but with radiation it would be something less than 10%.
1:59:57.845 --> 1:59:59.825
Atif Khan
It would be some unknown X, right?
1:59:57.995 --> 2:0:0.545
Eileen P. Connolly
Yeah, that's over setting, yes.
1:59:59.885 --> 2:0:8.795
Atif Khan
Whereas with the other biological assay, it's been characterized that it goes from 10% to 5% or whatever it is, there's some characterized reduction with the risk.
2:0:2.535 --> 2:0:2.785
Eileen P. Connolly
0.
2:0:9.5 --> 2:0:13.555
Atif Khan
So that's the difference is not 10% versus 0, that's not what's happening.
2:0:13.565 --> 2:0:16.475
Atif Khan
It's exactly so just to be clear. Yeah.
2:0:15.55 --> 2:0:16.215
Eileen P Connolly
It's relative research.
2:0:16.415 --> 2:0:29.445
John Williams
Gave this may sound inappropriate, but for that question, true, true and unrelated, we have to allow human beings which are adults, to counsel with the best of information with patients.
2:0:29.455 --> 2:0:44.485
John Williams
The decision in those little margins are going to be different from each patient to each patient, but I would argue that the biologic Test gives us very good important for a patient to make the best choice whether to do it or not and have better outcomes.
2:0:44.685 --> 2:0:53.285
John Williams
But I think when we narrow down to that shared decision-making human factors Trump the nuances of that Matt.
2:0:53.375 --> 2:0:55.5
John Williams
And that's much bigger aspect.
2:0:55.55 --> 2:0:57.625
John Williams
Having the information is critical.
2:0:57.875 --> 2:1:6.85
John Williams
Not having it, especially in patients that could benefit from it, in my opinion, is detrimental and harmful to patients.
2:1:6.675 --> 2:1:6.965
John Williams
All right.
2:1:6.915 --> 2:1:7.75
Alastair Thompson
Yeah.
2:1:6.975 --> 2:1:7.945
John Williams
We are at time.
2:1:8.545 --> 2:1:8.815
Gabriel Bien-Willner
Yeah.
2:1:8.825 --> 2:1:9.755
Gabriel Bien-Willner
Thank you very much.
2:1:9.765 --> 2:1:28.215
Gabriel Bien-Willner
The last two questions really to say, is there anything that you think is relevant that we did not discuss that should have been discussed with the evidence that that we did not present that should have been presented or listed in the bibliography?
2:1:28.225 --> 2:1:37.175
Gabriel Bien-Willner
I would just say if thinking about this, if you guys can think of anything else and you can send us an email with papers or something that we may have missed here.
2:1:37.315 --> 2:1:38.855
Gabriel Bien-Willner
Unfortunately, we are out of time.
2:1:38.865 --> 2:1:41.835
Gabriel Bien-Willner
I do want to thank you guys so much for this very lively discussion.
2:1:41.845 --> 2:1:42.5
Gabriel Bien-Willner
It was.
2:1:42.615 --> 2:1:48.685
Gabriel Bien-Willner
It was great information to take back, and I hope you guys are also got something.
2:1:48.695 --> 2:1:55.905
Gabriel Bien-Willner
I've been here, and I like to also thank the more than 120 or 30 people that that got to witness this.
2:1:55.915 --> 2:2:2.755
Gabriel Bien-Willner
Hopefully they got some of this as well, but we certainly did and this will certainly help us in, in, in drafting a policy.
2:2:4.145 --> 2:2:4.565
Alastair Thompson
Thank you.
2:2:5.795 --> 2:2:6.175
Eileen Connolly
Thank you.
2:2:5.945 --> 2:2:7.55
John Williams
Thank you for your work.
2:2:6.955 --> 2:2:7.435
Gabriel Bien-Willner
Thank you all.
2:2:7.65 --> 2:2:8.295
John Williams
It's not easy work.
2:2:7.245 --> 2:2:7.445
Brian J. Czerniecki
Yeah.
2:2:8.305 --> 2:2:8.945
John Williams
God bless you.
2:2:9.515 --> 2:2:9.635
Kimberly Van Zee
Yeah.
2:2:9.575 --> 2:2:9.675
Alastair Thompson
Yes.
2:2:9.645 --> 2:2:10.285
Atif Khan
Thanks a lot.
2:2:10.95 --> 2:2:10.505
Kimberly Van Zee
Thank you.
2:2:10.185 --> 2:2:12.395
Gabriel Bien-Willner
Yes, thank you.
2:2:10.345 --> 2:2:10.875
Atif Khan
Thank you.
2:2:10.615 --> 2:2:12.995
John Williams
But the but the most important things to do right.
2:2:11.95 --> 2:2:12.85
Alastair Thompson
Thank you for doing what you do.
2:2:14.105 --> 2:2:16.895
Gabriel Bien-Willner
And it thinks this point we're gonna conclude this meeting.
2:2:16.905 --> 2:2:19.395
Gabriel Bien-Willner
Thank you all once again for participating.
2:2:20.535 --> 2:2:21.435
Kimberly Van Zee
Alright, thanks.
2:2:21.835 --> 2:2:22.265
Alastair Thompson
Thank you, Sir.
2:2:22.375 --> 2:2:23.715
Gabriel Bien-Willner
Thanks bye.
