COMMENTARY

Randomized Data (Finally) on Partial Breast Irradiation

Kathy D. Miller, MD; Julia R. White, MD

Disclosures

February 05, 2019

This transcript has been edited for clarity.

Kathy D. Miller, MD: Hi. I'm Kathy Miller, professor and associate director of clinical research at the Indiana University Simon Cancer Center. Welcome to Medscape Oncology Insights. Joining me today is Julia White, professor and director of breast radiation oncology at The Ohio State University. Welcome, Julia.

Julia R. White, MD: Thank you for having me, Kathy.

Miller: This is a big year for radiation oncology. We have talked about partial breast radiation for a decade, maybe more. But until this year, really all we have had is single-institution cohort studies. We finally have randomized data. Get me out of suspense. Tell me about those trials.

NSABP/RTOG/NRG Trial

White: The trials tell us information. It codifies what we already knew about partial breast irradiation. As you know, many women want breast conservation, but the long radiation period becomes burdensome and then becomes a barrier, and they don't go through treatment.

Two big studies are reporting. In one from the NSABP/RTOG/NRG,[1] 4000 women were randomized to partial breast radiation over 5-8 days versus over 5-6 weeks. It looked to see whether it was equivalent. It's interesting because statistically, it was not quite equivalent in terms of outcome. But numerically, [the outcome] was about 0.7% (< 1% difference) at 10 years. It was the same with the likelihood of relapse anywhere.

If you look at all of these women with a median follow-up of a decade, overall there is less than 4% in-breast recurrence and about 3% distant metastases. Amazing.

Miller: They are doing really well.

White: They are doing amazingly well. For women who have a low-risk profile (ie, hormone sensitive, node negative, postmenopausal), I think partial breast irradiation is a good choice. This is really what the American Society for Radiation Oncology (ASTRO) has been saying in the absence of these data. Pick those patients who will likely have low event rates of cancer recurrences in the future and stick to that. I think that is what the data show.

Miller: Partial breast radiation is not one thing; it can mean a bunch of different things to different people. How did they deliver the partial breast radiation in this trial?

White: In the NRG trial, the radiation was standard whole breast irradiation. Most of it was done over a period of 5-6 weeks at 2 Gy fraction per day, which is what has been done in the United States for 40 years.

Partial breast irradiation can be done with the external beam method (with a linear accelerator, which every radiation department has) or as brachytherapy, where you insert radiation by a device in the breast temporarily and deliver radiation. Less than about 800 of our 2000 patients who got partial breast radiation had brachytherapy-based partial breast radiation.

Miller: Most of this was external beam. The set-up was similar to whole breast radiation but with different treatment planning.

White: Exactly. What is important—and it was not a planned analysis so I don't want to make too much of this, but—we have been asked so much in this trial [whether there] is a better method for partial breast irradiation. Quite honestly, we do see more event rates in the groups that got brachytherapy. Again, a minority of our patients [received brachytherapy]. But we feel more comfortable saying that the external beam is where we see fewer events. And it's what people have at access.

RAPID Trial

White: The large RAPID trial presented by our Canadian colleagues[2] had a different design than ours, but their data are very similar. Their outcome was very nice, within 2% and 3%, respectively, recurrence risks and a median follow-up of 8 years. But they are reporting about the toxicity from radiation. They do show how the radiation was done in external beam. Remember that these trials were designed a decade ago and we have gotten so much better. In a certain percentage of women who got partial breast irradiation, their cosmetic result was not as good as in the whole breast irradiation arm.

Miller: Tell me more about the Canadian RAPID trial. It probably is not as familiar to our US listeners as the NSABP/NRG/RTOG trial.

White: External beam in both trials was very similar. It was the same dose and used very similar "rules of the road" in terms of how the radiation was delivered.

Miller: The Canadian trial did not use the shorter scheme, what many of us call the "Canadian fractionation."

White: They did for whole breast irradiation. That was a big difference. I'm glad you said that. The whole breast irradiation in the Canadian scheme was a "Canadian fractionation," so, 16 fractions making it already shorter. In the larger NRG trial, that was mostly 5-6 weeks of whole breast radiation.

However, their trial had about 2000 patients and a different design. Ours was about 4000 patients. Nevertheless, we have 6000 patients to address this question. They are saying that it's not inferior to do partial breast irradiation in terms of cancer outcomes, in terms of survival and distant metastases.

However, they are reporting at the San Antonio meeting that they see slightly more significant toxicity in the partial breast irradiation arm. They also see the percentage of women who had a good cosmetic outcome moved down to a fair cosmetic outcome by 8 years.

Miller: How did they do partial breast radiation?

White: All external beam. We have learned a lot about partial breast irradiation since we started both of these trials. In these trials, we give radiation twice a day, thinking it would reduce the toxicity of radiation. But it's burdensome to patients and to clinical practices. Maybe it's too much radiation in one day. Maybe we should go back to once-a-day fractionation.

A lot of information has come out since we started both of these large trials in North America that tell us that we can figure out how to deliver it safely. Now that we know there are populations of patients for whom partial breast irradiation given over 5-10 days is a convenient, fairly equally effective treatment, I think that is where the new focus will be.

Optimal Candidates for Partial Breast Radiation Therapy

Miller: The good news is that we have a lot more data to inform our discussions and decisions with patients. They have a lot of options for how they get radiation, either whole breast [over] 5-6 weeks the way it's been done for 40 years; partial breast radiation with different techniques; or for some women, maybe even a consideration of not having radiation after breast-conserving surgery.

Whenever we have more data, decisions in some ways get easier and in some ways get harder, because they become much more individualized. Are there patients who you can envision coming to your clinic on Monday morning for whom you would not consider partial breast radiation?

White: I would not consider it for anybody who has [risk for a] high event rate of local, regional, or distant recurrence. Personally, [I would not consider it for] triple-negative breast cancer.

Miller: Even if it's a 1.2-cm node-negative tumor? Triple-negative is out for Julia.

White: I would not. The reason we ran the equivalence [test] in this NRG trial is because, as you know, there is always this debate about whether breast conservation is as good as mastectomy. After decades and decades, we finally have shown that, yes, it's just as good as mastectomy in local regional recurrence rates.

When we started to say, "Let's not treat the whole breast," we felt that we needed to say to women, "You can get part of the breast treated, and it's just as good as whole breast radiation. And by deduction, it's just as good as removing the breast." We didn't want anyone to feel like they were giving up [a benefit in] their risk for recurrence.

Miller: We did not want to lose benefits that we had gotten.

White: That was the whole mindset of it. In doing so, we did this very large trial, and we have to be honest. Relapse-free interval and in-breast recurrence did not meet statistical criteria for equivalence. Whole breast irradiation is slightly better.

Is that really meaningful in all patients? Patients who [may] have high event rates are the ones I personally worry about—that this might magnify those differences.

Miller: They have more to lose. They have a higher risk to start with.

White: Exactly. Low-risk patients in our study, by ASTRO consensus guideline, with a median follow-up of 10 years had a 2% in-breast recurrence risk— 2.3% with whole breast and 2.5% or 2.6% with partial breast irradiation. That is a slam dunk. That is great. They may not even need that radiation.

Miller: That was going to be my next question. Those are the folks that, when the event rate with partial breast radiation or whole breast radiation is that low, at some point we have to start talking about—who really does not need radiation?

White: That is what this trial did not do. The RAPID trial did a better job of saying they would just treat node-negative breast cancer in patients over 40 years old. They have a higher rate of hormone-sensitive patients. We wanted to say, "Let's take a wide swath of people who are getting whole breast irradiation and compare it with partial breast irradiation de facto." We did that.

It's not perfectly equivalent, but we can see very different event rates through these populations. I think the next step for radiation oncology in breast cancer is to follow our medical oncology colleagues and say, "This is a heterogeneous group of patients." If you even double the recurrence risk in a luminal A cancer, it's 5%. Maybe it's doubled and you omit [radiation]. I think there'd be a lot of women for this trade-off if you say, "You are not going to die of your breast cancer. You might have slightly higher risk if you don't get your radiation, but you can still get a second lumpectomy and keep your breast." I think that is a future question that we need to address.

Miller: When you get to address those questions, we will have you back. It is really fantastic to be able to start individualizing radiation decisions in the way we have tried to individualize other aspects of treatment.

White: We were a little bit behind in the game.

Miller: Great news for patients. We will have longer discussions in clinic to sort through what is best, but that is okay. Thank you, Julia, for joining us.

White: My pleasure. Thank you for inviting me.

Miller: Thank you to our audience for joining us for this fascinating discussion. This is Dr Kathy Miller from Medscape.

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