MolDX: Biomarker Testing for Risk Stratification in DCIS Open Public Meeting - August 27, 2025 - JE Part B

Jo Gilbertson

Good afternoon and welcome to Noridian's Open Public Meeting. My name is Jo Gilbertson, and I am one of the Medical Policy Specialists here at Noridian Healthcare Solutions.

We will be presenting proposed MolDX: Biomarker Testing for Risk Stratification in DCIS.

Before we begin the meeting, I'd like to make a few of the following announcements.

This meeting will be recorded. The recording and written transcription will be posted on our website following today's meeting.

All lines are currently being muted and will remain muted throughout the meeting.

Only those who registered to present will be allowed to comment on the proposed LCD today. For the presenters today, you are being allotted seven minutes to make comments. The reason for this was there were so many people that wanted to present on this and to add their comments that to get everyone in. At this time, we had to cut it down from 10 minutes to seven.

Your line will be open when it's your turn to speak. Make sure you are not on mute within your system or we will not be able to hear your comments. You should be prepared to begin your presentation immediately when called upon and will hear the moderator's voice when one-minute remains.

I do have everybody's presentation already included in Noridian's. So, all you will have to do is say next.

If at the end of your seven-minute time limit, your line will be muted, and we will move on to the next speaker in order to ensure that the system will be, excuse me, in order to allow all registered commenters time for their presentations.

We have added closed caption feature in real time for today's call. Please speak clearly to ensure that the system will be able to translate into captions for display.

As I had mentioned, the recording and transcript will be posted to our website.

By signing in today, you are giving consent to the use of your recorded voice and your comments. Please be mindful of sharing any personal health information during your presentation.

In addition to comments that are made today, all comments should be submitted in writing. All written comments received will be recorded in the response to comment article.

I will now turn the meeting over to Dr. Rajadhyaksha. Dr. Rajadhyaksha, you may begin.

Dr. Rajadhyaksha

Good afternoon and welcome to the Open Meeting of Biomarker Testing for Risk Stratification in DCIS. Please note that Jurisdictions JE and JF have the same draft LCD number, which is DL40142.

At this point, you know, I usually go over the policy, the proposed policy, but I will not in the interest of time today.

So, I'm going to invite the first commentator, Dr. Rachel Rabinovich, to please give a comment.

Thank you.

Dr. Rachel Rabinovich

Great, thank you so much for giving me the opportunity.

Next slide.

I just wanna point out that I have no financial or contractual relationship with Prelude or DCISionRT. I'm considered a national breast expert with an expertise in DCIS and radiation therapy.

Next slide. Next slide, please.

So, I just wanted to review because I've read through the LCD draft, and I think some things need clarification.

Nope. Back one. Back one slide, please. Yes.

That needs some clarification. So as of today, the only way a clinician or a patient can make an assessment about the value of radiation or measure that value is by using tumor grade, DCIS size, and patient age.

And these are tools that have not changed in over 50 years. And personalized genomic and molecular tools have revolutionized breast cancer already and are standard of care use in determining chemotherapy benefit. And these biomarkers were approved and paid for long before randomized trials confirmed their benefit in a 1A level test.

Regarding the DCISionRT test for DCIS, which is what we're discussing today. There have been multiple published analyses of over four international data sets separately and pooled that I've listed here. And I think in the LCD draft, it seems to ignore the fact that there have been multiple peer-reviewed publications demonstrating the efficacy, the data behind, and the value of the DCISionRT test in helping women and clinicians decide whether radiotherapy is of value. And this is a biomarker which really moves patient care forward beyond clinical pathologic features, which again have not changed in many, many decades.

So, there are many tools which are useful and I believe validated in determining prognosis of decision of DCIS, but it's very clear that the DCISionRT tool is the only one which demonstrates the ability to predict radiation benefit, not the oncotype DCIS tool that demonstrates just a 50% reduction across all patients. And so, this is a really unique and special thing about this specific biomarker.

So, I just wanna go through where we're at, RTOG 9804 was a prospective randomized trial that was actually stopped early, but it demonstrated that we can identify a group of women that by traditional clinical pathology have about a 10% risk of recurrence without radiation and that risk is reduced by 8% with radiation. And it's considered a standard of care medical recommendation today to offer women radiation omission, but you're asking a woman to give up an 8% local control benefit based on clinical pathologic criteria.

And if you take those 9804 group of women, and this was recently published by Frank Vicini in the Seminal Radiation Oncology Journal, half of those patients are actually high risk when you use the biosignature by Prelude, demonstrating a much larger benefit of radiation that on average is about 13%. Again, this is a personalized biosignature tool, so a woman gets an individual score with her personal risk of recurrence with or without radiation. So, this tool helps prevent undertreatment in women who otherwise it is considered a standard of care medical option to offer no radiation.

And I'll point out that if it demonstrates that it's a low risk score, it improves upon RTOG 9804 because now you're not telling a woman that maybe she has to leave an 8% risk of recurrence on the table with radiation omission, but you can identify those patients who have a one or less than 1% risk of recurrence that they're foregoing with radiation omission.

And similarly, if you look at high-risk patients by clinical pathologic criteria that traditionally we always recommend radiation, 28% of them are reclassified by the Prelude test to be low risk and not needing radiation and this prevents over-treatment.

And patients with concordant clinical pathology and the DCISionRT test, whether it's high or low, gives great assurance to the patient and the clinician that they're making the right choice.

And I just wanna go back to that bullet where it says 51% of patients are reclassified as high-risk. I just want to point out that without the biosignature, you're actually asking clinicians and patients to do a coin toss.

Next slide, please.

I have been involved with NRG for three decades and have proposed a clinical trial, which has gone through a three-year rigorous process and has been accepted by the National Cancer Institute. It's going to be NRG CC-016, a randomized trial that will randomize patients with a low risk DCISionRT score to radiation or no radiation, regardless of grade, age, or tumor size within the validated group.

This has been so compelling that ECOG-ACRIN has joined on board, and the purpose of this test is to reach level 1A evidence after having multiple peer-reviewed trials, which includes a subset of a prospective randomized trial.

Jo Gilbertson

One-minute remains.

Dr. Rachel Rabinovich

Pardon?

Jo Gilbertson

One-minute remains.

Dr. Rachel Rabinovich

Thank you.

So, I just want to comment for one minute.

I reviewed the LCD, and I have to tell you, I'm kind of shocked by some of the criterion in your coverage guidance that the patient must not be considering mastectomy to get a biomarker.

All patients have the option of considering a mastectomy, and it's always paid for.

Not having RT in the same breast previously, that would be an amazing opportunity to use a biosignature, which would say the patient could undergo another lumpectomy and safely forego radiation.

In your criteria of what the test must have, it says you need multiple published studies. This test does have that.

And you also point that it has to be as good as other risk stratification biomarker tests, and I believe it does.

And then at the very end, there's also.

Jo Gilbertson

Excuse me, thank you for your comments, but your time is up. If we have time, we could come back.

Dr. Rajadhyaksha

Thank you, Dr. Rabinovich. Sorry about the short time.

I'd like to now ask Dr. Chirag Shah to make his comments.

Dr. Chirag Shah

Sure. Next slide, please. So, thank you for the opportunity to present.

I am a breast cancer Radiation Oncologist. I see many, many DCIS patients every year.

I am also the Division Chair of Radiation Oncology at Allegheny Health Network and have been involved with more than 200 peer-reviewed manuscripts with a focus on breast cancer and DCIS and I've been involved with much of the work on biomarkers and DCIS.

Next slide, please.

Dr. Rabinovich did a great job of explaining the clinical data supporting the use of DCISionRT as a biosignature. I had the privilege of being the first author of this study, and we can kind of click to show the rest of the slide please, that looked at what the clinical impact was. And I think really my focus in this conversation today is to talk about what this means for patients. And what this study looked at was the use of the biosignature and how it impacted patient care.

And so, we looked at basically how patients were thinking about radiation before and after the test, and what was the radiation change in terms of recommendations.

This study was over 2,000 women treated for DCIS at over 60 sites, both academic and community practices. So, this could be extrapolated broadly.

And what we saw as the key takeaways, first of all, that the use of this test changed the recommendation in radiation by 38%.

That means almost two out of every five women with DCIS who have this test will have a change in their recommendation based on it.

Next slide, please.

I think just as importantly, this isn't a test that goes one way only.

This is a test, this slide, shows goes both ways.

There are patients who were recommended radiation, who got results from the biosignatures that they couldn't get from clinical pathologic or other features, who were recommended not to receive radiation after DCISionRT.

And then just as importantly, preventing undertreatment, you had a cohort of patients who were not recommended radiation, who had testing, who were then recommended radiation.

So, 31% initially not recommended RT were recommended at post radiation and 41% who were initially recommended radiation were not.

Next slide, please.

Can we go to the next slide, please?

There you go. Thank you.

What this study shows is that basically amongst clinical pathologic low risk patients, those ones that we say in the guidelines, they'll use clinical pathologic features, you know, 43% of them actually had a change in recommendation based on DCISionRT, which you wouldn't have gotten with clinical pathologic features.

And this is the key that Dr. Rabinovich mentioned as well, is that the Red Journal paper shows you that clinical pathologic features are no better than a coin flip. And as a doctor, I certainly don't want to be making guidance for my patients and informed discussions based on a coin flip. And this test is giving me much more than that.

Next slide, please.

Can we see the next? There we go.

That next slide shows that basically when you look at the factors that actually drove radiation recommendations, it was the DCISionRT test and patient preference.

This is not a binary test. This is a test that we use as part of shared decision making and informed discussions with patients. And what you see is those two are aligned.

We use this test to the service of our patients to help them make informed, educated decisions that are in line with their values.

Next slide, please.

So, this slide shows basically that as we have an increasing score, we see an increasing recommendation for the receipt of radiation and how we are on a continuum, not a binary distribution when it comes to yes or no. 29% of patients still were recommended radiation after a shared informed discussion with their patients.

Next slide, please.

You know, one of the things as a Radiation Oncologist we deal with is the idea of a boost or giving an extra dose of radiation to the area where surgery is done on top of whole breast radiation.

And again, we've commonly used clinical pathologic features, but we haven't really found a group that truly needs or doesn't need a boost.

And this is something where the biosignature DCISionRT gives us a new piece of information, the residual risk subtype.

Patients have an increased risk of recurrence even after lumpectomy and traditional radiation where we might want to give them a boost to get their risk of recurrence down further.

Next slide, please.

And this is from that recent publication that Dr. Rabinovich mentioned, which is we're identifying patients with the biosignature of a high risk of recurrence even after lumpectomy and radiation. So, if you look at this information, you have low risk patients and we're seeing this pink in the far right.

That's about five to 10 percent of patients using RTOG-94 and almost 20 percent using Sloan-Kettering nomogram who have this residual risk subtype of almost 15 percent risk of recurrence with radiation and a 42 percent risk of recurrence without radiation.

These are patients who, based on clinical and pathologic features, may be offered omission of radiation, which would be a gross undertreatment and something that couldn't be identified without this assay.

Next slide, please.

So, in summary, you know, I share you know, Dr. Rabinovich's disappointment with the draft LCD, is I don't think it really addresses the data, the clinical utility of the DCISionRT assay.

It doesn't address published literature showing the utility, including the three DCIS trial, which is a randomized trial that was run and that was then shown you be able to stratify patients and their benefit from radiation with the assay.

It really has no understanding the draft LCD of residual risk and what the importance of that is in preventing undertreatment, nor does it assess the clinical utility based on the PREDICT trial showing that the test leads to a huge change in recommendations regarding radiation therapy.

For me, the DCISionRT test is a standard of a care option that I discuss with my patients, every patient I see with DCIS.

Depriving them of that would be depriving them of optimized, informed, and shared decision making that other things like clinical pathologic features can't do.

Jo Gilbertson

One minute remaining.

Dr. Chirag Shah

I actively participated in reviews for this assay when they were initially not covering it and I will continue to do so, to really do so for my patients to make sure we advocate so that patients are getting the care they need and the informed and shared decision-making tools available to them.

Thank you.

Dr. Rajadhyaksha

Thank you, Dr. Shah, for your comments.

I would like to now invite Dr. Kristi Funk to make her comments.

Dr. Kristi Funk

Good afternoon.

My name is Dr. Kristi Funk. I'm a surgical breast oncologist in private practice now for 23 years with extensive experience in the management of DCIS.

Thank you for this opportunity to share my thoughts on draft LCD DL41044. I do not have any conflicts of interest to report.

I must respectfully oppose the draft policy.

The LCD as written strongly conflicts with clinical practice and it undermines patient autonomy, specifically because the coverage indications include that the patient must, one, not be considering mastectomy, she isn't sure yet. And two, quote, "she must have a formulated treatment plan that includes radiation therapy and consents to its use." She's not ready to consent yet. Why?

She wants more personalized information. She deserves to assess her risk tolerance in light of a personalized bio risk score, which may dramatically change how she feels about either radiation or her choice of surgery.

This draft is not an appropriate coverage determination regarding DCISionRT in practice today. It should be retracted.

Next slide.

Let's define the problem.

Due to the adoption of widespread mammography in the 80s, the incidence of DCIS skyrocketed from less than 2% when DCIS was largely an incidental finding in mastectomy specimens of no particular concern to fully 15 to 20% of all screen-detected breast cancers.

In 2025, you can see here, we expect 56,500 new DCIS cases, which as you know, are stage zero cancers that when they stay that way, they never spread, they never kill you, they never need chemo. So, what do they need?

This DCIS explosion has spawned decades of over-diagnosis and over-treatment in almost two million women with zero change in breast cancer survival rates.

We create surgical morbidity.

I even sometimes do bilateral mastectomies with bilateral reconstruction over one centimeter of fairly indolent DCIS because all women are told the standard of care is radiation or else you have to do a mastectomy.

Is that really true?

We cause radiation toxicity.

We push endocrine therapy, causing premature menopause, quality of life issues, sometimes ending their hopes of childbearing, all in the name of creating local control so an invasive recurrence doesn't happen. But most of the time, it doesn't happen. So, whose DCIS will recur as a threat?

Next slide.

Enter the 1990s. We tried to refine local therapy. The VNPI aimed to select low-risk patients for excision alone.

That's good.

The problem is the clin path features in the VNPI like tumor size, margin-width, path-grade necrosis, patient age, they're not always reproducible in larger, more ethnically diverse populations. In fact, the VNPI oversimplifies DCIS biology, as does the MSKCC DCIS nomogram.

Today, neither of these is endorsed by consensus guidelines like NCCN, ESMO, ASTRO.

Nomograms have been superseded by prospective trial data and genomic assays.

Next slide.

Indeed, since the 2010s, we've entered the genomic era and we make decisions using genomics, paying attention to margin with and patient preference, but patients can't figure out what they prefer until they have an accurate assessment of their personal risk for recurrence and invasive cancer risk with and without radiation, which is the exact genomic data that DCISionRX gives me and them.

Next slide.

We limit morbidity with genomic data.

And as I know you know, DCISionRT enables identification of women who may safely avoid radiation therapy.

Multiple peer-reviewed papers show identification of patients with minimal to no benefit from radiation. Like this PREDICT study, it looked at 2007 DCIS patients and showed that genomic data changed the radiation recommendation in almost four out of every 10 patients. And it goes both ways.

Next slide.

Specifically, 31% initially told, nah, you can skip radiation based on your low clin-path features, like it's grade one and only a centimeter and you're seventy-five. And then we get the genomic data and oh, let's rethink this.

You would actually benefit from radiation quite a bit.

On the other hand, 41 percent told, you better get radiation, we're able to skip it.

You might ask, is radiation really that big of a deal?

Next slide.

It certainly can be. During treatment, women need to take time away from work and children. Their skin starts to get irritated with redness and peeling and dryness. Their breast swells. They start to get tired, go to bed earlier, can't work, or think quite as well. Their breast starts to hurt, and they notice changes in the areolar color and nipple sensitivity.

Moving on to next slide.

Weeks to months after finishing radiation, they still have these persistent skin changes. Their breasts gets firm and starts to shrink. Either they can have delayed wound healing and sometimes develop lymphedema of the breast or arm and rib discomfort. The gifts just keep on giving.

So next slide.

Months to years later, often permanently we see chronic lymphedema of the breast or arm, persistent breast asymmetry needing surgical correction, pulmonary effects, cardiac effects, secondary cancers, including angiosarcomas and lung cancer, fractures of the rib, and then complicated surgery and reconstruction in the event of a future breast cancer or recurrence or need for more surgery.

So yes, avoiding radiation that does not improve your survival has a lot of upside.

Next slide.

The draft LCD neglects to assess the impact of biomarker testing prior to surgery. I use DCISionRT before going to the operating room. Why? It changes what I do.

For example, if we get a result that says, "Hey, you have a 5% of recurrence without radiation, 3% with it." She decides, no way, no radiation. I'm going to get wider margins. And that also might lead to a concurrent oncoplastic reduction.

Jo Gilbertson

One minute remaining.

Dr. Kristi Funk

So now all of a sudden, on the front end, before surgery happens, the patient and I participate in shared decision-making, balancing oncologic safety and cosmetic outcome.

Next slide.

On the other hand, what if we do want radiation? When DCISionRT identifies patients with strong benefits from radiation, we can plan for it.

Maybe she wants intraoperative radiation, a one-and-done shot in the OR that requires coordinated planning with RAD-ONC, and I need to know what I'm doing.

Some women may be so motivated to avoid the recommended radiation that they choose mastectomy based on their values and preferences.

Last slide.

In conclusion, I use DCISionRT and routine clinical practice and I believe both the quality of cancer care during treatment and the quality of life during survivorship will diminish without access to such a test.

Thank you for your time.

Dr. Rajadhyaksha

Thank you, Dr. Funk.

At this point, I would like to call Dr. Roberto Diaz to make his comments.

Dr. Roberto Diaz

Good afternoon and thank you so much for this opportunity.

I also have no financial conflicts of interest with Prelude, and I also respectfully oppose the draft LCD. I'm of Radiation Oncologists at the H. Lee Moffitt Cancer Center in Tampa, Florida.

I've probably treated anywhere from one to 2,000 breast cancer patients. I probably treat one to 200 breast cancer patients every year.

Next slide, please.

Personalized radiation for DCIS; precision reduces recurrences and spares harm. When facing DCIS, patients and physicians confront a critical decision, pursue post-lumpectomy radiation or not.

Radiotherapy significantly reduces recurrence risk in DCIS, a fact proven by rigorous evidence. Yet, it offers no benefit for distant metastasis or overall survival, and not every patient needs it.

The key question that we're posing is, how do we target radiation to those who will benefit while sparing others its burdens, as it was clearly articulated? By embracing personalized medicine and tools like DCISionRT, we can answer this with unprecedented precision, improving outcomes, and minimizing harm.

The evidence that has been previously discussed from RTOG 9804, but that study illuminates the quote unquote good risk DCIS.

This landmark phase-three trial provides clarity for what is a good risk DCIS.

A mammographically detected, low, or intermediate grade tumor, under two and a half centimeters with surgical margins of at least three millimeters.

Patients were randomized to radiation or observation and after 15 years of follow-up, the results were striking. Without radiation, a 15% local failure rate, with radiation less than half, only 7.1 percent local failure rate. This means that 85 percent of these patients would not have benefit from radiotherapy, but 15 percent do benefit.

Administering radiation to all risks unnecessary side effects for the majority.

Instead, I would argue genomic tools like DCISionRT empower us to identify that 15 percent of patients who need radiation while sparing the rest from the reducing healthcare costs.

As has been addressed, the VNPI and MSKCC nomograms are historic attempts at risk assessment, but they're seldom used in practice, they're not on NCCN guidelines, and there's inconsistent evidence about risk and radiation benefit or omission.

Next slide, please.

Personalized radiation for DCIS, why precision matters.

DCIS treatment, as we discussed, reduces local recurrence, but not distant mets or survival.

Not all patients need radiation, yet there is a blanket approach that risks unnecessary side effects.

Solution, DCISionRT, a molecular tool identifies who benefits from radiation enabling personalized care.

The benefits include minimizes harm, reduces costs, optimizes outcomes by tailoring treatments to individual risk.

Next slide, please.

So, when we address this residual risk in the low-risk DCIS, even with radiation, 7% of these low-risk patients face a recurrence.

DCISionRT can pinpoint these residual risk cases, enabling tailored interventions like a radiation boost or rigorous endocrine therapy compliance.

This precision ensures patients receive the right treatment intensity, maximizing protection against recurrence while avoiding overtreatment.

So, this, we can use this information from DCISionRT to inform a patient about shared decision with the clinician and choose to proceed with treatment with radiotherapy.

Next slide.

So, targeting radiation with data-driven precision.

There is, as I mentioned, I will categorize DCIS, as we mentioned, the low risk from the RTOG 9804.

There's other, also the all-comers, which are patients who have larger tumors, high grade DCIS, ER-negative, or narrow margins. These have about a 30% recurrence risk without radiation.

DCISionRT identifies patients more likely to benefit from radiation, about 60% of these patients with high in-breast tumor recurrence.

DCISionRT identifies patients less likely to benefit from radiation, about the 40% with a low risk of in-breast tumor recurrence.

Therefore, DCISionRT improves risk stratification compared to clinical pathology.

And as I mentioned about the residual risk DCIS, there are about 7% of the low-risk patients, even with radiation, who will recur, and about 15% of patients who are all-comers.

So DCISionRT can identify this residual risk subtype with a high recurrence rate after radiation.

So, to those patients, I would offer a boost, definitely encourage them if appropriate for them to adhere to endocrine therapy, and absolutely ensure post-treatment screening like mammography and MRI.

Next slide, please.

The power of personalized medicine.

In today's era of personalized medicine, we must move beyond a one-size-fits-all approach.

By integrating clinical pathological data, we're not throwing that away. We need to integrate clinical pathologic data with the genomic insights from a molecular tool like DCISionRT, patients and physicians can make informed, individualized decisions.

This approach respects the unique biology of each patient's tumor, ensuring treatment that is neither excessive nor inadequate.

So why risk harm without benefit?

Treatment benefits must outweigh the risks.

DCISionRT clarifies whether radiation is necessary.

If the test shows minimal recurrence risk, then the patient can confidently forego radiation, avoiding its side effects and costs.

Jo Gilbertson

One minute remaining

Dr. Roberto Diaz

But if it reveals a high recurrence risk, with half of these recurrences, by the way, progressing to invasive breast cancer, patients gain the certainty needed to pursue radiation with conviction.

This is not just about treatment. It is also about empowering patients with data to take control of their action.

DCIS treatment demands precision.

DCISionRT is a game changer, offering clarity where uncertainty once prevailed.

By leveraging this tool, we can target radiation to those who need it, spare those who do not need it, and optimize outcomes for all.

Let us embrace this opportunity to deliver smarter, safer, and more effective care.

For patients, it's the difference between unnecessary burden and tailored protection.

For physicians, it's the confidence of evidence-based decision.

We must choose precision.

And those are my comments, and once again, expressing my disappointment with the draft of the LCD.

Thank you.

Dr. Rajadhyaksha

Thank you, Dr. Diaz.

Our fifth speaker is Dr. Beth Dupree.

Dr. Dupree?

Dr. Beth Dupree

Thank you very much.

Thank you to all of my colleagues who've gone before me today because I don't have to repeat anything that has been said but I, I have done lectures to Prelude years ago when we were introducing this technology I have not done so in several years, but I just wanted to disclose that right away. Clearly the draft LCD mischaracterizes biomarker testing it has been-

Go to the next slide, please.

It's been really difficult to watch this process because the NCCN guidelines clearly do not promote or validate any clinical tests for DCIS.

They recommend taking the information that we have and doing shared decision-making.

There is clear evidence that DCIS DCISionRT works across ages and real-world impact is shown conclusively.

So, I really think the LCD either needs to be retracted or revised to reflect clinical reality.

And I'm going to go through the steps to help you understand this.

Next slide.

Next slide.

Next slide.

Thank you.

The draft misinterprets the biomarker as binary treat or no treat, which is, it's really continuum. You look at this from beginning to end.

As a surgeon, we are the captains of the breast cancer ship.

We are, the we're the ones that get the patients first. And like Dr. Funk, I sit down with my patients every single time and go through the risks, benefits, and alternatives to their procedures.

But I need to have genomic information on a tumor at that time to be able to counsel my patient appropriately. And having the DCISionRT from the beginning allows me to help that patient to come up with a plan to treat their cancer exactly as they would like to with the appropriate information.

It provides a continuous decision score.

So, it gives us these nuances in shared decision making, whether someone has a 0.8 or a nine could change their treatment management based upon their age, the size of their breast, and their desires for their own treatment course.

I have participated in, I can't even tell you how many ALJ reviews without compensation at all, and I'm going to continue to do so. And I believe only one of them we did not find in favor of the insurance participant that it was appropriate for that person to get that test.

So, DCISionRT is reasonable and necessary, and I believe that any woman diagnosed with DCIS should be given this information at the beginning of her journey, not waiting until she has a treatment plan for radiation, because it undermines my ability to give that patient the appropriate surgical information about what they can do for themselves.

Next slide, please.

Next slide.

The DCISionRT clinical value lies in its ability to stratify recurrence risk.

And so, you can look at someone not based upon just their age or their stage of their grade.

What we know with the clinical pathologic information is that it's based on what the pathologist sees.

We know that not every estrogen receptor responds the same way, and we know that there's a biological behavior of tumors that none of us can know by looking at a slide under a microscope and waiting for a pathologist to give us an answer.

So, having the genomic information, understanding that we can look at a patient's tumor and help that patient prepare a path for their cancer care allows us to give better treatment.

And I believe that the DCISionRT gives us that information so that we can then educate our patient even before they meet with radiation oncology and then come back again to decide what's the most important aspects of her care that she needs to know in order to choose the right surgery?

Next slide.

So, the current LCD draft undermines the patient's choice and NCCN guidelines of shared decision-making. It absolutely takes that away.

We, we really need to be able to look at how our patients, how our patients can benefit from this information and the way that they benefit from this is, if we can resect low risk disease to negative margins, those patients are gonna potentially get the same benefit from just receiving anti-estrogen therapy.

And radiation therapy at that point could prevent them if they did get a second cancer later from getting radiation therapy in that breast and then needing a mastectomy.

So as written, it basically wants to give us a one size fits all approach where it's treat or no treat.

And if you enforce this fixed 5% cutoff for benefit, you've literally taken away the ability to have shared decision making with our patients.

When I started my surgical practice almost 40 years ago in medical school, mastectomies were, all the patients were offered mastectomies and axillary node dissections. We then moved into lumpectomies radiation therapy.

And to me, we've gone from taking a shotgun to breast cancer, to being able to pinpoint and target specifically how we treat each and every cancer patient.

And this has been an evolutionary process.

And for me, I've always been a skeptic when some new technology comes out and I have thrown a lot of new technologies and a lot of new breast nuances to the curb because they didn't make a difference for patient care. They were just basically companies looking for a purpose.

Next slide, please.

Next slide.

So, you listed a Dr. Shah's data showing that women under 50, women 50 to 60, and women over 70, every single group, there was a difference of over 35% change in how to treat. And this, and this information validated what I had found out.

Next slide.

So back in 2017, I came back from the American Society of Breast Surgeons and talked to my radiation oncologist, Dr. David Beyer, who was at the time the most recent past president of ASTRO. And I said, David, I said, I've identified a test that I believe could make a difference in our patient care. And he said, well, let's take a look at 20, 30 patients and see whether it changes our clinical management.

And you can see just by the colors on these slides where the highs and the lows of the grade and the DCISionRT do not match up.

Next slide.

Jo Gilbertson

One minute is remaining.

Dr. Beth Dupree

Next slide.

Next slide, please.

One more slide.

Next slide.

So this one we had a total 48 patients and this is where Dr. Beyer said that he believed that this test was going to make a difference and he said, "I understand now why you want to get this and why you want this at the beginning," because of the 16 patients that were high-risk clinically, they were low-risk DCISionRT and could safely avoid radiation therapy. 11 went from intermediate to low risk and six were low-risk and went to high-risk and six intermediates went to high-risk where we then treated the appropriate patients. So, we weren't treating any less patients. We were just avoiding radiation in the patients that could, and we were able to eliminate radiation therapy in over 50% of patients that could avoid radiation therapy.

Next slide.

Next slide, please.

Again, keep going. Go to my final slide.

Next slide.

Age-based evidence standards are arbitrary. The LCD Medicare age is not scientifically valid determinate.

Over 1,500 women under the age of 65 receive Medicare benefits and are diagnosed with DCIS.

So, this current draft is not just inappropriate, it is discriminatory to these women, these, of these four million women that are under 65 on Medicare. They would not be given the benefit of utilizing this test to be able to have shared decision-making and allow them to have a play, you know a play of really significant role in their cancer care treatment.

So, thank you for your time.

I hope that you take these considerations very seriously and that the LCD draft is either revised or thrown out or somehow made to really reflect what our patients need, which is the opportunity to have the information upfront, at the time of their diagnosis so that they can make an appropriate treatment plan and follow through with it.

Thank you.

Dr. Aparna Rajadhyaksha

Thank you, Dr. Dupree.

I apologize.

I think there's a little brief delay between moving the slides, and we'll try our best to accommodate that with time.

The next speaker is Dr. Shawna Willey.

Dr. Shawna Willey, are you on?

Dr. Shawna Willey?

All right.

I guess we'll move on to the next speaker and come back.

Jo or Krista, you all want to move to the next one?

Okay.

The next speaker is Dr. Aimee Gallant.

I'm hoping I'm pronouncing your name correct?

Dr. Aimee Gallant

Yes, that's great.

Hi, thank you so much.

I appreciate the opportunity to be able to speak.

We can go to my first slide, please.

So, it's just the introduction, so I'll get started.

So, my name is Fleure Gallant. I'm a Radiation Oncologist at Maimonides Cancer Center in Brooklyn. I'm the clinical Director of Radiation Oncology.

I subspecialize in breast radiation oncology where over 95% of my practice is breast cancer patients and have been in practice for over 11 years.

I would like to respectfully show my disappointment about this LCD draft, which I do not think is an appropriate coverage determination and think it should either be revised or retracted.

I have been trained and I'm from Canada, where I pride myself in being very selective and thoughtful about any test that I use. I'm very mindful to make sure that if I'm going to use something, it has to be something that is going to make a difference in patient care.

I would say that initially I was slow in the uptake of using genomics for DCISionRT, but now with the very strong data that's been presented by my colleagues, I have great confidence in the utility of this test, and I could say that I now find it difficult not use it because I find that it has become so integral and important in determining patient management and it certainly provides significant information above and beyond what we get from clin path alone.

So next slide, please.

So, I'm going to be focusing primarily on the residual risk subtype, which is a novel biosignature which identifies patients with DCIS who still have a higher risk of a local recurrence even after they have lumpectomy and radiation therapy.

And this was published by Dr. Vicini in our premier radiation oncology journal, the Red Journal.

Next slide please.

So, as you can see here, the DCISionRT score stratified patients, low risk where there is little to no benefit of radiation.

There's an elevated risk of group where there is substantial benefit of radiation and patients are lowered to a risk of recurrence, you know, to 5% or less.

And then what you have in on the far right is this residual risk group where they have a substantially higher risk of recurrence, upwards of 40% with surgery alone.

And even after radiation, although there is a substantial benefit to radiation, as you can see between the blue and the purple bars, even after radiation, they remain at an elevated risk of recurrence at about 15% even with radiation.

Next slide.

Here, you can see that these, these results are identical, whether or not we use the initial cross-validation cohorts with UUH and UMASS or without, so the data remains consistent amongst the different cohorts that have been used to validate the test.

Next slide, please.

And there is statistical concordance as well in terms of the results showing no difference in the IBR rates for DCISionRT between the low, elevated, and residual risk groups between the study cohorts.

Next slide, please.

So, this is what the patient receives and what the clinician receives when they get the score. So, this residual risk group is 9.2 and it has a special designation where, again, you see a much higher than average risk of recurrence with surgery alone 42% and a 15% risk of recurrence even after radiation, usually we quote patients a less than 5% risk after, after radiation therapy.

So, when a patient is making her decision between having breast conserving surgery or mastectomy, seeing these numbers might in fact influence her decision as to whether or not she wants to proceed with mastectomy or not.

And I'll get into that in a little bit with some cases.

Next slide, please.

So, this is looking at patients who we traditionally felt were "low risk," and you'll notice that is in quotations, based on clinical pathologic factors.

And you can see both looking at the RTOG 9804-like patients, patients that are considered low-risk in the MSKCC nomogram, or just based on grade, higher age, and other low-risk clin path factors.

Within all of these patients that we would think, looking at the patient in clinic, seeing their pathology and the details of their imaging, within these patients that we think are low risk, we see a pretty substantial proportion of patients who are elevated risk and even having high residual risk.

Next slide, please.

So, this is a case, a patient that I saw preoperatively, 69-year-old female with a small DCIS, and we assume negative margins, meaning the RTOG-like low-risk criteria. And she came in very fearful of having a breast cancer and came in wanting bilateral mastectomy, which was as alluded to by some of my colleagues, sometimes patients are very fearful and just want to go straight to bilateral mastectomy even for these very small potentially indolent cancers.

You know, both the surgeon and I felt that this seemed like overkill to have bilateral mastectomy for such a small non-invasive disease, so we were encouraging her to consider breast conservation with or without radiation, which we often will omit radiation in older patients with small tumors.

So, in the end, to help with the shared decision-making and help guide the patient, we ordered a DCISionRT and much to our surprise, she actually did have this residual risk score of 9.2. And then for her, in seeing these numbers, this actually confirmed her preference.

Jo Gilbertson

One minute remaining.

Dr. Aimee Gallant

Indeed, she did want a mastectomy, but in the end ended up having unilateral mastectomy.

Whereas we thought, you know, that's a perfectly reasonable decision choice, but also, we would have still felt comfortable doing breast conserving surgery and radiation if she wanted.

But this shows a dramatic change in the course of events where I probably would have told this patient she didn't even need radiation after a lumpectomy and negative margins, not knowing that she actually was high risk.

Next case, so this is a similar case, a patient over the age of 70 with multiple comorbidities who didn't want to have breast conserving surgery and radiation because she was worried about her heart and she wanted a mastectomy.

The surgeon was not keen to bring her for surgery and we ended up getting the score which showed she did indeed benefit from radiation.

So, we went forward with the breast conserving surgery and radiation approach, completely sparing her heart.

So again, a patient that I probably wouldn't have treated with radiation but knowing that this is a patient who would have had a 28% risk of recurrence in her 80s, we were very happy that we gave her that additional radiation benefit.

Next slide, please.

So, the residual risk type definitely highlights patients who are at high risk and having this information before the surgery can be very helpful both for the surgeon in terms of the amount of margins they want also for the radiation oncologist when they're considering their boost dose. Often, I will give a higher boost dose to such patients and it really adds to shared decision-making.

Thank you very much for your attention.

Dr. Aparna Rajadhyaksha

Thank you so much for your comments, we're going to try Dr. Willey one more time.

I think she had difficulty getting off mute. Hopefully, she can this time. Good luck.

Dr. Shawna C. Willey

Can you hear me?

Dr. Aparna Rajadhyaksha

Yes, we can.

Dr. Shawna C. Willey

You can hear me? Oh, fabulous. Thank you. I apologize for the technical issues.

My name is Shawna Willey. I'm a practicing breast surgeon in Washington, D.C. metropolitan area. I've been in practice for over 35 years. I've been practicing breast surgery exclusively.

You can go to the next slide.

For 25 years.

Can you advance the slide? Thank you.

This shows my credentials, next slide.

There's some basic statistics around DCIS and we've heard some of them in the form of the slides that we've seen today, but some that I would like to highlight is number four, which is that there are no clinical pathologic features that have proven reliable for predicting in which patients we could omit radiation.

And I especially like to identify the last line, which says that neither radiation nor mastectomy, nor anything that we do can reduce the recurrence rate for DCIS to zero.

And I think this is an important thing to relay to patients and is important in this discussion around this draft policy, which, by the way, I also oppose, as do the prior colleagues' presentations.

Next slide.

We are in the age of personalized medicine, and every breast cancer is biologically unique.

We've learned this from the genomic tests for invasive breast cancer, and now we have one for non-invasive breast cancer, and yet there's a proposal to limit its use. But every patient is also unique. Every patient brings to their DCIS their own history, their own particular family history, and also their vision and feelings about what their treatment should be.

I like to use the DCISionRT, I use it in all my DCIS patients to inform my patients about their individualized risk, because that is not possible using clinical pathologic features alone.

Historically, I've used the VNPI and the Memorial Sloan Kettering Nomogram, but I no longer use it because I have a much better test to help predict what's going to happen to my patients.

Those were valuable when that's all we had, but those are basic epidemiologic tests that cannot be extrapolated to an individual.

So, the DCISionRT test allows for a framework for us to have a discussion with our patients to allow for shared decision-making so that the patient can help balance their goals for efficacy of treatment versus toxicity.

Next slide, please.

We've heard several examples, but I'm gonna give you my own examples of, of really three categories of tests.

We can have a very low-risk test, a test that shows that patients need radiation or we can have this residual risk subtype.

I had a patient who was in her late 60s who came in with a core biopsy that showed DCIS.

The first words out of her mouth was that she wanted a mastectomy. Of course, I then had to delve into what her reasons for having a mastectomy were. And those reasons were because she'd had a family member who had radiation, and she didn't want radiation because her family member had had toxicity from the radiation.

So, we decided together that we would send a DCISionRT test on her core biopsy and along with the radiation oncologist who might have treated her we found that she was very low risk.

She could avoid radiation and, in that patient, we saved her breast, and she is now about five years out without any evidence of recurrence and is very happy that she did not have to have radiation.

I think we have more patients that are probably in the orange category where it's not quite as low as we'd like it to be, but it's not as high as in the residual risk subtype.

And that is a group of patients where we really do need to sit down, we look at the report, we look at what the risk of invasive cancer is, we look at what the risk of non-invasive cancer is, both with and without radiation.

And this is where you really find out what your patient's risk tolerance is because I may say that a decrease in risk of recurrence of 2% is not worth getting radiation, but for a patient that may well be worth getting radiation.

And so, I think that's a dialogue that we really need to have, and we really need to inform our patients about. In addition, we have this residual risk subtype, as you've heard about before.

I have a patient that I did a lumpectomy on and I did not get clear margins.

We sent her surgical specimen off for a DCISionRT, and she came back with a 9.9, the highest score I've ever seen.

She was very able to process this information, and I had not gotten clear margins, so she was going to need another operation.

And we decided together that for her and her risk tolerance, it would be much better for her to have a mastectomy rather than a re-excision and radiation, because then she could get her recurrence rate down to a level that she could tolerate.

Next slide.

You've heard from both radiation oncologists and from surgeons. And as Dr. Dupree said, patients generally start with the surgeon. That's generally the first oncologist that they see because most of what we do is to dictate the care. We're the captains of the ship, as she said, and what we do affects the downstream care.

I looked at our own use of DCISionRT at Inova and we've been using this test since 2018.

We've ordered it in 853 patients, 25% of whom had Medicare.

And I would think that that is a large number just for one health system to be using this test and to be able to inform 853 patients what their eventual treatment should be.

Should they get adjuvant radiation? Should they have an endocrine therapy? Should they have a mastectomy?

I would hate to see that almost a thousand patients would be denied that opportunity to be able to use real data about their DCIS to help them make decisions. Surgeons

Jo Gilbertson

One minute, please.

Dr. Shawna C. Willey

Thank you.

Surgeons really play a critical role in tailoring care. So, we could put somebody in a high-risk protocol or we could follow them without radiation, for instance.

Next slide.

So, I would say that the draft is really a black and white draft. We don't think that that's what reflects real practice.

We cannot rely on clinical pathology risk factors or assessments, because if we do, we're practicing cookie cutter medicine and women deserve better than cookie cutter medicine especially for a disease that will not change the overall survival of those women.

Next slide.

So, one size fits all really does not equal optimal care.

We want the right treatment for the right patient at the right time and as a breast surgeon I feel a grave responsibility to be able to lead this shift towards precision medicine and individualized breast cancer management.

I strongly oppose the draft as it is written.

And if it goes through, I think it's a huge step backward for the women in our country who have DCIS.

Thank you for your time, and I apologize for the technical glitch.

Dr. Aparna Rajadhyaksha

Thank you, Dr. Willey.

The next speaker up is Dr. Janie Grumley.

Dr. Janie Grumley

Hi, I'm Janie Grumley.

I'm the surgical breast oncologist here in Santa Monica. I'm the Director of the Comprehensive Breast Program at Providence St. John's Health Center and I have been in practice for over 14 years in breast oncology.

I have no financial relationships with Prelude or any other companies or any other conflicts of interest.

I do truly believe, just as everybody else has said, that this draft is not appropriate coverage and should be retracted or at least revised.

You've already been presented with a multitude of data showing utility of DCISionRT.

So, I'm not going to bore you with rehashing all of that.

Breast cancer treatment, as we all know, is a multidisciplinary discussion.

And as a surgeon, decisions about radiation impact surgical care, as many have already highlighted.

Biomarkers have become a complementary part of the shared decision-making process in breast cancer treatment.

And early-stage breast cancer, specifically DCIS, the consequences of overtreatment, can be just as detrimental as under treatment with potential cost to patients and to society.

Clinical pathologic information alone, as we have heard from so many already, cannot determine optimal treatment for our patients. It has not been reliable.

Molecular testing is what is available today. It is not used, however, in isolation when we treat patients.

With many of the peer published data already, DCISionRT has become a very useful tool for physicians like myself, when we talk about decisions and guiding patients for the best possible individualized treatment plan.

We know that one size doesn't fit all, just as Dr. Willey has just said.

Based on current available research, DCISionRT has been shown to be reliable.

It is a really useful tool that helps us look at patient risk and help guides our treatment.

Clinical pathologic features that we've used in the past, like those Van Nuys and there's been many years of criticism for a lot of those nomograms and hasn't helped us determine what that individual's risk might be.

DCISionRT has been used in my practice and has significantly helped in discussing treatment options with patients.

It is something quantitative that we can present to the patients. Instead of you may be at higher risk, we can actually give you what we think is a numerical risk.

This is particularly helpful in the older Medicare population.

Because as we all know, as we get older, quality of life is important, and when we weigh the risks and benefits of treatment, quality of life has to be considered.

This draft does not accurately reflect the current breast cancer practices.

Next slide.

Next slide.

Thanks.

So currently, DCISionRT is set for patients who need to make difficult decisions regarding their care.

You've heard lots and lots of examples already. Radiation is not without its risk. It is not just a little sunshine. There are significant risks associated with treatment, but if there is no clear benefit, we really don't want to cause risk in those patients.

However, if there is clear benefit, that is something that we want to be able to make a bit, we want available to our patients.

So, molecular tests like DCISionRT provides an additional tool in helping that decision making process.

If we determine a patient's high risk, patients may opt for a different surgical options like the many patients have opted for mastectomy.

Now mastectomy is not without its risks.

So, we wanna know that it's actually worthwhile before we do it.

While others who wanna avoid radiation come in saying they wanna have mastectomy and without fully understanding some of the risks associated with mastectomy, they will just express that they want a mastectomy. But if we can show them that they may be at low risk and can omit the use of radiation in their treatments, this is something that may be very useful in their decision-making process.

This LCD also had noted that this should not be used in patients who are considered for mastectomy.

That's absolutely the patients that need to be, that this test would be helpful in because that may change their mind and reduce their anxiety.

Without these quantitative tests, these decisions become so much more difficult.

Our traditional tools have not always been reliable.

It's like trying to figure out who is gonna be a Nobel Prize winner and who is gonna be somebody who's working at McDonald's, by just looking at their physical features.

There is no way that we could determine the full extent of the cancer without understanding the molecular risks.

Currently in my practice, patients with low-risk DCIS can safely avoid radiation.

So, as long as there is no other concerning pathologic features.

While others who have low risk pathologic features and a high DCISionRT score would seriously consider radiation options in hopes of reducing recurrence.

Patients have found this information very helpful when they're faced with this decision.

We would never make critical health decisions without all the available information.

I wouldn't go into surgery without pathology, so why would a patient go into and have radiation without all the information about their disease, including their molecular risk?

And in current economic times, we need to be economically responsible.

From a society perspective, DCISionRT is a more economic and more efficient way of providing patients who need radiation with radiation and eliminating radiation from those who may not benefit.

I thank you for this opportunity to comment.

And I do believe that this draft needs, doesn't reflect this current, our current clinical practices and needs to be revised.

Thank you.

Dr. Aparna Rajadhyaksha

Thank you, Dr. Grumley, for your comments. I'd like to now call our ninth speaker, which is Dr. Eileen Connolly.

Dr. Eileen Connolly

Thank you. Can you go ahead with the next slide?

So, I'm Dr. Connolly. I'm a radiation oncologist at Columbia University.

Can you hear me? Sorry. Thank you.

I'm a radiation oncologist at Columbia University.

I treat; I'm the lead for breast cancer and I've been treating breast cancer patients exclusively for the last 13 years. I have no disclosures regarding Prelude DX.

Next slide. Next slide, please. Hello. Next slide. Okay. So, yeah, that's it.

So, I won't bore you again with a lot of the details that have already been gone over by my colleagues in great detail.

I just want to summarize that I think that this LCD, as written, conflicts with the NCCN guidelines, as others have stated, in that we want to make patient decisions should be done in a shared decision-making framework. And this LCD conflicts with this, as well as current clinical practice, as it conditions coverage on a predetermined patient choice, a predetermined patient plan, and undermines patient autonomy.

Therefore, I really, I believe that it should be withdrawn or substantially revised.

As others have already stated, the proposed LCD requires that patients in order for coverage for DCISionRT have an RT plan in place and consented to its use and then intend to forego use of radiation if it's determined that they are sufficiently low-risk by a predetermined low-risk set point of 5%.

There are multiple concerns that I have with this.

One is the pre-commitment requirement, which is very unworkable and inconsistent with NCCN guidelines.

Two, it misunderstands the intended use of biomarkers.

Three, its outcome contingent coverage, which undermines patient choice.

And four, it supplants but does not complement clinical practice.

So next slide, please.

So, my key concerns, go ahead.

One is the pre-commitment requirement, which is unworkable and inconsistent with guidelines.

As I've said already, this, as the LCD is currently written, it requires that you have a radiation plan, the patient has already consented to it and that the patient is in agreement that they will forego radiation should they be found to be low risk.

As multiple other people have already stated, this is completely unworkable.

Patients come in and they need this information to make decisions including the surgery that they'll have and whether or not they need radiation.

So, it's impossible for us to have this ahead of time when we're planning to order it.

Second, it misunderstands the intended use of a biomarker.

DCISionRT provides us, as many have already said, with significant information regarding a patient's risk and benefits to radiation, but it's intended to inform and not replace clinical judgment and patient preference.

So, it is not intended to be the sole or principal determinant of radiation. It's an overreach of the LCD to state that it should be.

Clinicians routinely integrate these types of biomarkers into our decision making and it's important for the patient to have this information to finalize their choices.

Next slide please. Continue.

So additionally, the way the LCD is currently written, its outcome contingent coverage, meaning that the patient has to already have set in their mind what they'll do before they're even able to get the results of the test.

This is inappropriate and in odds with NCCN emphasis on individual decisions.

You're taking away a patient's decision in order for them to be able to get the test.

And it really is inappropriate considering the goal of the test is to help a patient make decisions.

Also, number four, it supplants but does not complement clinical practice.

As the LCD is written, the idea is that you would use this test completely superseding patient, physician expertise and patient wishes, meaning that you use the test and that's the decision that's made.

And this is inappropriate, as I've already stated.

Next slide, please.

So, the requested revisions, I would request they remove the pre-commitment clause and replace it with something that says that along the lines that DCISionRT should be used to help inform decisions. And it's not intended to be, you shouldn't have a predetermined result in mind before you order it.

You should clarify that this is a tool to be used in addition to clinical pathologic factors as well as patient preference and not as a sole determinant of radiation.

You should decouple the coverage from the ultimate treatment choice or payer-imposed absolute benefit cutoff.

It should not be up to the payer what the risk tolerance of a patient should be.

This is a physician-patient choice that should be made together.

And lastly, I propose that you adopt more practical documentation standards, including indications, intended use, how it will affect patient decision-making, and the important role in joint decision-making.

So, thank you very much for allowing me to speak.

Dr. Aparna Rajadhyaksha

Thank you, Dr. Connolly.

I'd like to now ask Jennifer Douglas as the tenth speaker to make her comments.

Jennifer Douglas

Hi there. Can you hear me?

Dr. Aparna Rajadhyaksha

Yes.

Jennifer Douglas

Excellent.

So, thank you for allowing me to speak today.

I'm going to offer you a bit of a different take.

My name is Jennifer Douglas. I'm a DCIS survivor, author, and a patient advocate.

And I'm here again also to urge you to reconsider this LCD to limit or remove coverage for DCIS biomarkers like DCISionRT.

Biomarker testing is the standard of care for invasive breast cancer and the recent research shows that tests like DCISionRT are superior to clinical pathology to show whether DCIS is low risk or high risk.

I will start by sharing my personal story with you, then share what I've seen here in patient groups, and then also offer a few final thoughts on the future of personalized breast cancer and how critical this is to all breast cancer patients.

The day before my 42nd birthday in 2019, I was diagnosed with DCIS.

It was my second annual mammogram.

In a flash, I went from being a healthy mom of two teenage boys to being a cancer patient.

My mind swirled with decisions that I never wanted to make.

While my DCIS was caught early and low grade, I quickly learned that stage zero didn't mean zero challenges.

My surgical and oncological team encouraged me to consider a lumpectomy plus radiation, especially since my genetic testing revealed I had no genetic variants.

I read the research, considered my options, and decided that since my DCIS was small, I would opt for that treatment pathway.

My radiation team highly encouraged me to proceed with whole breast radiation plus a boost since I was in my early 40s.

I didn't know about DCISionRT at the time, and I was willing to do whatever I needed to do to reduce my risk of recurrence. I had no idea how hard radiation would be.

The 20 treatments caused me significant fatigue.

I was a healthy young woman and the fatigue devastated me. In addition, I experienced significant burning and

Dr. Aparna Rajadhyaksha

Hello, can you hear me?

Jo Gilbertson

Hi, yes, I can.

Dr. Aparna Rajadhyaksha

Thank you. We apologize. I don't know what happened. We got bumped off, but we will start off where we left off.

Thank you.

Jennifer Douglas

Hello, can you hear me?

Dr. Aparna Rajadhyaksha

Yes, we can. Sorry about that. I guess the GoToWebinar just kicked all of us out.

Jennifer Douglas

Okay. Well, at least it wasn't me.

I'm gonna go back to where I thought I was. I'm just talking about how hard radiation was.

So, I had no idea how hard radiation would be. The 20 treatments caused me significant fatigue.

I was a healthy young woman and the fatigue devastated me.

In addition, I experienced significant burning and peeling twice.

Radiation was one of the most challenging parts of my DCIS treatment.

If I could have safely skipped it because of my tumor biology indicated I was low risk I might have made a different decision.

And in fact, in 2022, did you want me to stop?

Dr. Aparna Rajadhyaksha

No, please go ahead.

Jennifer Douglas

Okay, great.

In 2022, I needed to have another lumpectomy on my non-cancer breast for a suspicious lesion.

It turned out to be benign, and so I didn't need radiation.

It's back to my life and a few shocking to me how much radiation had impacted me.

My journey was so hard, I decided to write a book about it.

And then I joined the online world of patient advocacy.

And over the last five and a half years, I've learned a lot about talking with other DCIS patients.

I'm an active member of lots of DCIS communities, member of some DCIS specific patient support groups, and I lead support groups as well.

And I can tell you radiation drives surgery decision-making.

Nearly daily in these groups, I see patients opting for a mastectomy so they can avoid radiation.

And often these decisions are driven by a fear of radiation and the side effects they may endure during and after treatment.

Additionally, many of us may not have access to modern radiation treatment facilities within a short distance of our homes.

And so, they need to do radiation, but that means significant time financial toxicity for not only them and their families. While the treatment time itself may be short, the round trip can take hours out of their days mean patients and their families cannot work.

So, the question about impact as breast cancer treatment continues to advance, do DCIS patients deserve the option to request a biomarker test that may help them and their medical teams make better treatment decisions that go well beyond clinical pathological features?

The future of oncology involves using a patient's tumor biology to optimize cancer treatment plans.

We've seen all of that in the presentations and thank you.

I just ask that if DCIS treatment is to be advanced, we need access to the advanced tools.

This includes precision making, precision medicine, and decision-making tools that examine our tumor biology.

Thank you so much for allowing me as a patient to share my voice here and for making a decision that make benefits all DCIS patients and ensures their access to modern biomarker tests.

Dr. Aparna Rajadhyaksha

Thank you so much and sorry for the interruption again.

We'd like to now invite Dr. Lawson, Laura Lawson, to make her comments.

Dr. Lawson?

All right, hopefully we can come back to Dr. Lawson. Let's go to the next speaker.

I'd like to invite Alastair Thompson to make his comments.

All right.

Dr. Ashish Chawla, are you on?

Dr. Vincent Reid?

Donna Pinto?

Donna Pinto

Hi there. Can you hear me?

Dr. Aparna Rajadhyaksha

Yes, we can. Thank you.

Donna Pinto

Okay, great. Thank you so much.

Hello, everyone.

I want to say thank you to all the excellent presenters and thank you for giving me the opportunity to speak today as a patient advocate on behalf of the more than 50,000 women diagnosed with DCIS every year in the United States.

I concur with the evidence to revise the LCD draft, and I want to start by saying my name is Donna Pinto.

I'm the founder of DCIS 411, a website and blog which provides support and resources for an informed, individualized, and integrative approach.

I also lead online DCIS support groups with thousands of women.

And like Jennifer said, there's daily discussion what drives surgery and treatment decisions.

It's very, very challenging and a tremendous anxiety. I speak with women every single day, so this is very, very important.

Why I believe DCISionRT is so important. Not only does DCISionRT give a woman and her family tremendous peace of mind, this test can provide physicians the scientific evidence to feel more confident in supporting these challenging treatment decisions, both for someone like me with low-risk DCIS, as well as for a woman who is at a more elevated risk.

I believe DCISionRT plays an important role in shifting the paradigm away from the needless emotional trauma, the worry, overwhelm, confusion, uncertainty, intimidation, and fear, as well helping to reduce the widespread problem known as overtreatment of DCIS.

I believe every woman diagnosed with DCIS deserves DCISionRT.

To give some background about how I came to this understanding.

15 years ago, in 2010 at age 44, I was diagnosed with intermediate grade DCIS. I'd never heard of this before.

I was told it was a pre-cancer, but the standard of care treatment is similar to invasive cancer. Lumpectomy, plus seven weeks of daily radiation therapy or a mastectomy.

This did not sit right with me. Both options sounded extreme and frightening.

The treatments felt more dangerous than the diagnosis. I started researching immediately.

Within two days, I found a Medscape article where well-respected breast cancer doctors were discussing a controversy about overtreatment of DCIS and the need for biomarker.

I researched non-stop for nearly two years.

And then I created DCIS 411 with the goal of helping women diagnosed with DCIS slow down and understand the issues as well as current research.

In addition to the short and long-term side effects mentioned, two of the biggest issues are, one, discordance on agreement of grade among pathologists is very high.

Studies show 25 percent or more disagreement, and grade is therefore unreliable.

I always tell women to ask their doctor about DCISionRT to get more information. Number two, the radiation therapy can only be used once.

If later there is an invasive cancer, mastectomy is then deemed necessary versus lumpectomy and radiation.

My background includes being a patient advocate since 2016 on two multi-million-dollar DCIS research projects, both nationally and internationally, the COMET study, which compares surgery to active monitoring for low-risk DCIS, and then the PRECISION project standing for prevent ductal carcinoma in situ invasive overtreatment now.

When I learned about DCISionRT in 2018, I was thrilled. To know 50,000 women a year would no longer be potentially over-treated as one size fits all, as I was told, or considered like me against medical advice if you choose to decline radiation therapy.

It's very, very difficult to be in that situation.

With DCISionRT, every woman now has the opportunity to know their true risk as an individual and make the most informed decision with scientific backing as well as their doctor's blessing. This is incredibly valuable.

Every woman can now have peace of mind in making these serious life altering treatment decisions.

Every single one of the 50,000 plus women annually diagnosed with DCIS would benefit tremendously from DCISionRT.

For their mental, physical, and financial wellbeing, this test is a necessity.

It should be ordered with ease by every physician treating them with DCIS, and it should be covered by Medicare as well as every insurance company.

If I had had radiation therapy 15 years ago, as my doctor recommended, standard of care recommended, the nomogram, and the VNPI recommended, I would have had all the harms and zero benefits.

It's been 15 years, I never got invasive cancer, and I've been able to maintain a high quality of life and health, which is extremely important to me.

One final thought, with the current knowledge and research about DCIS, to not make this test easily accessible for all women diagnosed with DCIS on biopsy, my personal opinion is this is unethical and potentially medical negligence.

Thank you for reconsidering the LCD draft with the important information presented today.

Thank you.

Dr. Aparna Rajadhyaksha

Thank you so much for your comments. Dr. Nadia Zachariah, you're up next.

Dr. Nadia Zachariah

Hi, thank you for the opportunity to speak. I'm Nadia Nasara Zachariah.

I'm a breast surgical oncologist with Baptist Health in South Florida.

I would like to add to all the excellent data-driven presentations that we've heard with a physician testimonial.

I respectfully oppose the draft to the LCD as it conflicts with and undermines physician-patient shared decision-making.

As a breast surgeon, I sit with women every week who are facing a new diagnosis of DCIS.

They're otherwise healthy, who are suddenly asked to make life-changing treatment decisions such as breast conservation versus mastectomy, radiation versus no radiation.

DCIS is a heterogeneous disease, and we know that some patients are at low risk for recurrence while others are at much higher risk.

However, the challenge is that traditional clinical pathologic factors often don't give us enough clarity to guide these nuanced decisions.

DCISionRT has become an essential part of my practice.

I use it in every single DCIS patient consultation.

This test provides individualized recurrence risk and radiation benefit estimates and ensures that patients are not subjected to overtreatment with mastectomy or radiation they may not truly need, nor undertreatment where risk is underestimated recurrence is far more likely.

The benefit's not only theoretical and let me share one of my patient examples.

I had a 56-year-old woman who underwent excisional biopsy for atypical ductal hyperplasia which is a high-risk benign lesion and at the time of surgery is upgraded to DCIS unfortunately with a positive margin.

She was adamantly opposed to radiation and without DCISionRT she felt like her choice may have been a blind gamble. However, we discussed this test, and we had to make the decision to undergo rate decision versus mastectomy.

DCISionRT showed that she had an extremely low risk of recurrence and the data further clarified her true risk.

So, she was able to make a treatment decision with confidence that align with both the biology of the disease and her values.

Without this tool, she probably would have undergone a mastectomy that she really did not need.

Time to time again, I see DCISionRT empower patients and prevent unnecessary procedures and possibly radiation.

And it prevents unnecessary costs to our healthcare system.

It reduces likelihood of over-treatment, such as a mastectomy or radiation in low-risk patients and prevents undertreatment that can lead to recurrence, re-operation and additional downstream costs.

In short, it's not just a test, it's a great tool that makes care smarter, safer, more cost-effective, and most importantly, patient centered.

If this tool were no longer covered, many of our patients would lose access to this individualized decision-making.

We would be forced back into making broad recommendations based on incomplete information, and that means more of our patients would be at risk of unnecessary mastectomy, more patients would be receiving radiation they don't need, and others might be inadequately treated and face recurrence, all are outcomes that we should be working to avoid.

To me as a surgeon and as a patient advocate, the value of DCISionRT is undeniable.

It allows us to practice true precision medicine for DCIS and it has transformed my way, the way that my patients and I approach these difficult choices.

My urge coverage to be maintained for this test, not just for the sake of innovation, but because it truly changes patients' lives, reduces unnecessary intervention, and delivers far more responsible healthcare.

Thank you.

Dr. Aparna Rajadhyaksha

Thank you so much for your comments.

Our next speaker is Dr. Troy Bremer.

Dr. Bremer?

Dr. Troy Bremer

Thank you, and just to note, there were multiple people who were not able to speak earlier who had mic issues.

Dr. Aparna Rajadhyaksha

Yes, we'll get back to them as soon as the mic issues are resolved.

Thank you for letting us know.

Dr. Troy Bremer

Thank you.

So, my name is Troy Bremer.

I'm the Chief Science Officer for Prelude DX.

I appreciate the opportunity to present in this open meeting today for DCIS biomarker testing.

Next slide.

So, clinical pathology has been used for a long time, over 25 years, to help assess patient risk.

Over this time, treatment has been refined for surgery and radiation therapy, and there has been a consistent focus on de-escalation.

Today, it's not unusual to hear a treatment goal of 10% for IVTR at 10 years.

It's often espoused.

And there are tools like the VNPI and MSKCC's DCIS nomogram that have been tried but have had inconsistent evaluations in their studies.

These tools have inconsistently identified patients with lower 10-year IBE risks and consequently have not adopted as a standard.

Today, RTOG 9804 criteria is currently recommended by NCCN guidelines, but not as a black and white decision, but as part of shared decision-making for assessing low risk and considering RT omission.

Next slide.

I'm sorry, next slide.

Thank you.

The clinical pathology-based risk assessment studies often identify that low-risk patients have higher risk than a target 10% of 10 years is important, however, that clinicians and patients together are making shared decisions today that use clinical pathology-based risk assessment along with the patient's risk tolerance and treatment preference.

The biomarker test that further risk stratifies patients with low-risk clinical pathology will improve shared decision-making and help to prevent undertreatment.

Next slide.

Thank you.

Here we can see the DCISionRT test and I'm sorry, is the slide gone or is the session gone?

Dr. Aparna Rajadhyaksha

We're still here. I'm not so sure what's going on with the slide right now.

Let me double-check.

Dr. Troy Bremer

Thank you.

Dr. Aparna Rajadhyaksha

Dr. Bremer, apparently there's a delay or lag in getting the slides loaded.

Are you, can you go on without the slides being loaded?

Dr. Troy Bremer

I can try.

The data is helpful to see with-

Dr. Aparna Rajadhyaksha

Yes, I agree with you 100% and we're trying our best to get it on.

So, if you hold on for one minute hopefully it does come on. Let me see what I can do.

Dr. Troy Bremer

Okay, thank you. Great.

Krista Babbitt

My apologies, I lost total connection, so.

Dr. Troy Bremer

Thank you for getting the slides back. It would have been hard.

Appreciate that.

So, in this slide I'm just focusing on the fact that you can see that test is showing consistent reclassification of patients from low-risk clinical pathology criteria like RTOG 9804 to high-risk by DCISionRT, at least higher DS scores.

And you're seeing that in multiple different cohorts, UUH/UMASS, the Kaiser Permanente group, SweDCIS randomized clinical trial, and then a Combined Cohort that also includes Royal Melbourne Hospital.

It's all about a significant reclassification rate.

Also, these patients had a high risk of recurrence as was published.

Go to the next slide.

So, in a recent publication in the Red Journal, about half of patients who are meeting a variety of different clinical pathology criteria for low-risk or reclassified with high risk and have high tenure recurrence risks, also they have a significant benefit from radiation therapy.

And we'll go on into this in more detail.

Next slide.

Importantly, when these clinical pathology tools were evaluated in a multivariable analysis with DCISionRT using its continuous decision score, not a categorical group, only the DCISionRT test was significant for its little breast recurrence risk after breast conserving surgery without radiation, while the clinical pathology-based risk assessments were not significant for IBR risk.

Likewise, when you consider the patients who are treated with breast conserving surgery plus radiation therapy, again, the DCISionRT tool, the residual risk subtype in specific, was statistically significant for IBR risk, again, after treatment with BCS plus RT, and after accounting for the clinical pathology tools in multivariable analysis.

The tools were not statistically significant for IBR risk, only the test was.

So, what these analyses are showing is that the DCISionRT test is adding novel information not obtained from any of these clinical pathology tools which are both continuous and categorical assessments when compared to these tools in the overall population.

It is also interesting to note when you talk about the overall population that considering two studies, the SweDCIS study in the low DS scores patients and the Vicini publication that also had a large combined cohort and presented patients with low DS scores that in a meta-analysis, a simple analysis of those two results, the absolute risk difference in patients treated with and without radiation was 2.6% and had narrow 95% confidence intervals of 3.7%.

Again, what that's showing is that in the overall population, the test is identifying patients that are lower and higher in their risk and in these patients who have lower DS scores, that they did not have a statistically significant difference. They had a low-risk difference with or without radiation and that had a narrow confidence interval for those results.

Next.

Jo Gilbertson

One minute remaining.

Dr. Troy Bremer

So, when further looking at the limitations of clinical pathology with DCISionRT as a comparator, it's notable that about 50% of patients meet low-risk criteria for a variety of these tools.

In a recent publication, when assessing these patients who had low-risk criteria, the test reclassifies about half.

These reclassified patients had about a 20% risk and pronounced benefit.

The corresponding patients, interestingly, that had low-risk CP and low DS scores had low 10-year risks without radiation and no significant difference in 10-year risks with radiation.

Next slide.

Finally, when you look at this in clinical practice, the DCISionRT test has been assessed in a prospective study of 2007 patients.

As has been mentioned by several presenters today, it was in over 50 centers.

Importantly, we wanna talk about the subset of those patients that had low risk criteria by measures such as RTOG9804 or ECOG5194.

31% of patients who had these kinds of low-risk criteria who had initially been recommended no radiation were subsequently recommended radiation after using the DCISionRT test.

And in contrast, 49% of these patients who had low-risk clinical pathology who were initially recommended radiation were subsequently not recommended radiation after using the DCISionRT test.

In summary, the test in the study population that was prospective showed in clinical practice, there was about a 42% change in the treatment recommendations for patients who had low risk clinical pathology.

Next slide.

So, in summary, there are a number of issues in the structure with the proposed draft LCD, its conflicts with clinical practice today, and the use and proposed use of biomarker testing in the draft LCD.

There's also a number of issues that are inconsistent with literature or omit information that is present in literature, and we respectfully request that these be addressed and the draft LCD be withdrawn presently. Thank you.

Dr. Aparna Rajadhyaksha

Thank you, Dr. Bremer. Our next speaker is Dr. Frank Vicini.

We are hoping a couple of people who are having tech issues can resolve them and on, but for now, Dr. Frank Vicini is our last speaker. Thank you.

Dr. Frank Vicini

Well, hopefully you can hear me now.

Dr. Aparna Rajadhyaksha

Yes, we can.

Dr. Frank Vicini

I'm a radiation oncologist. Oh, great. In Michigan, can I have the next slide?

Excuse me. Next slide.

I'm also requesting that the draft LCD be withdrawn, I'll explain why, hopefully presenting some new data for everyone.

Next slide.

I've been a radiation oncologist for over 35 years now.

I've also been an examiner on a radiation oncology boards for over 20 years.

So, I certified radiation oncologists to treat breast cancer.

While tools like the VNPI and MSK nomogram have been used in the past, they are not currently used nor recommended or superior to our RTOG 9804 criteria.

Next slide.

Now, some of this will be a review, so hopefully I'll breeze over it.

Next slide.

So, you know, 9804 and ECOG 5194, while they identified a low-risk group, these patients also have a significant benefit still from RT, as we've seen.

Next slide.

And when compared to ClinPath, the new manuscript which I just had published, which on the first author shows that the DCISionRT test has significant risk stratification.

However, the test has consistently shown in multiple studies, as we've seen, that it reclassifies about half of the patients compared to 9804 and that these patients have a high risk of recurrence still.

Next slide.

The test was also previously compared to the MSK nomogram and showed that the DCISionRT test was statistically significant.

And in a previous publication of mine, we showed that the DCISionRT elevated and residual risk groups were significant factors as we've heard after accounting for ClinPath factors individually.

Basically, the data show that the DCISionRT test biomarkers are providing significant and unique value over ClinPath features alone.

Next slide.

I presented this comparison of ClinPath, next slide, at the ASTRO conference in 2023, which led to the publication, which I'll show you now.

And it basically looks at, as you'll see, a combined cohort of patients, and we compared the DCISionRT test to ClinPath.

Next slide.

This is the actual publication that just came out in the Red Journal, as was mentioned a couple of times now already.

I know there's a lag here. I'll wait. Yes, this is the publication, as I mentioned, that came out.

And what it does is it clearly shows the limitations of ClinPath criteria compared to the DCISionRT test, and I'll walk everyone through it.

Next slide.

As Dr. Bremer just mentioned, we've been using ClinPath in various ways, various criteria shown here to judge whether or not to give radiation therapy after lumpectomy.

And of course, they've been inconsistent and inappropriately applied.

And certainly, one of the problems as mentioned was grade.

Next slide.

So, what we did, so we can get through this pretty quickly for everyone, as we pooled the cohort of 926 patients that were published in the validation studies for the DCISionRT test, and we compared the application of the test to various ClinPath criteria.

Next slide.

So, this just shows you on the left, the DCISionRT test applied to the same 926 patients, identifying a low and a high-risk group, and then in the middle 9804 and MSKCC on the right.

And again, these are the same 926 patients showing you that there are different risk stratifications.

Next slide.

So as an example of the problems with ClinPath, when we applied 9804 criteria, there were 473 patients that were defined as low risk.

But when we looked at their 10-year outcome, we still saw a statistically significant reduction in the risk of local recurrence, despite the fact they were identified as low-risk by 9804 criteria.

Next slide.

And just as importantly, when we applied the DCISionRT test to these same 473 patients, as has been mentioned multiple times, it reclassified 51% of the low-risk patients into high-risk patients.

Next slide.

And just as critical, when you look at the outcome those high-risk patients, they had a significant reduction in the risk of local recurrence with radiation therapy.

Again, they were identified as low risk using 9804 criteria. Next slide.

Now just as important is that you do have some concordance using the molecular test to identify low-risk with 9804 low-risk and these patients clearly did not have any benefit from radiation therapy at 10 years. Next slide.

But just to be thorough and not to pick on 9804 since I was involved in the study, we looked at all of the different ways to classify patients as low risk using 9804, MSKCC, VNPI, various age groups, and ECOCs.

And what we found, as you can see here, there was a consistent reduction. Excuse me, there was a significant change in the profile in these patients, we identify 50% or more of the patients at high risks when you use the DCISionRT test and benefited substantially from radiation therapy.

Next slide.

At the other end of the spectrum, again, looking at high-risk patients, next slide, we saw a similar concept.

In other words, patients who had high-risk ClinPath using these tools were commonly reclassified in about a third of the time by the DCISionRT test as actually low-risk and did not have a benefit from radiation therapy at 10 years.

So again, these are real data and patients in the four validation studies.

Next slide.

So just to summarize here, multiple publications have shown us we've seen that about half of the patients with low-risk ClinPath are actually high-risk.

This is important in clinical practice where we're misclassifying patients and possibly inappropriately under or over treating them.

The test clearly identifies patients with high-risk ClinPath as low risk.

This highlights the inconsistency in using clinical pathology and the benefit from the DCISionRT test to prevent both over and under treatment and is extremely helpful in shared decision-making as a physician and for patients as well as we've heard earlier.

Thank you for your time.

Dr. Aparna Rajadhyaksha

Thank you Dr. Vicini for your comments.

At this point I'm going to ask the specialist, the MPSs, if anyone else got to join in.

Jo Gilbertson

Hi, this is Jo Gilbertson, and I'm not seeing anybody that we need to go back to, as I don't see them in the group at all.

Okay. We can go over the closing steps.

Next slide please.

So, thank you Dr. Rajadhyaksha.

In closing, we're just going to do the next steps in our process.

Next slide please.

The comment period for this proposed LCD will remain open until August 31, 2025. All comments to be considered by our medical directors for the proposed LCD must be submitted in writing.

Written comments can be to policydraft@noridian.com or mailed to the address on your screen.

Comment information for our proposed LCD is located on our website at noridianmedicare.com. Upon review of the comments, our medical director will either finalize or retire the proposed LCD, responses to comments will be viewable, in the response to comments article.

Please monitor our website or register for the listserv notifications to informed of actions taken on our proposed LCDs. Dr. Rajadhyaksha, do you have anything else that you would like to say before we end this meeting?

Dr. Aparna Rajadhyaksha

Thank you everyone for your comments.

We apologize for all the technical difficulties. We did our best to mitigate it.

For the commentators who could not be present due to technical issues, we still invite you to make your comments in writing so we can address them. Thank you so much again for everything.

Jo Gilbertson

Goodbye everyone and have a great rest of your day.