IN-SITU BREAST CARCINOMA: RADIATION ONCOLOGY CONSIDERATIONS, MARSHA HALEY, MD 1

Transcription

1 MARSHA HALEY, MD 1 Good afternoon. So I m going to give an overview of radiation therapy in the management of DCIS. And overall the goals of radiation therapy in managing this disease are to allow breast conservation, prevent DCIS recurrence and prevent invasive recurrence. And it s important as Dr. Johnson mentioned to notice that increased improving survival is not one of the goals of radiation therapy for DCIS. So I m first going to go over some of the seminal trials with the radiation oncology for DCIS. Dr. Johnson had mentioned some of those in his chart but we ll go over those in a little bit more detail. So probably the original trial was NASBP-B17, they looked at over 800 patients with DCIS, patients had to have negative margins, they were randomized to lumpectomy plus or minus radiation therapy and at 12 years the risk of recurrence was decreased by 50% both in the invasive and non invasive components. The UKCCR also did a trial with over 1700 patients, they used a 2x2 factorial design, they looked at lumpectomy plus or minus radiation, plus or minus tamoxifen and the radiation therapy was found to reduce the local failure by 43%. The EORTC looked at over 1,000 patients with DCIS again negative margins, patients were randomized to lumpectomy plus or minus radiation therapy. The risk of local recurrence was reduced by 47% with radiation therapy. Half of the recurrences were invasive. They found that the risk of recurrence was increased with younger aged, positive margins, and higher grade.

2 MARSHA HALEY, MD 2 Dr. Bhargava had mentioned the Van Nuys Prognostic Index and what they proposed is that you could use certain factors to determine whether or not radiotherapy was needed. So in their estimation a low score was indicated that after lumpectomy radiation would not be needed. An intermediate score was that radiation therapy would be needed after a lumpectomy and a high score meant that the patient should have a mastectomy for the DCIS. The VNPI has not been adopted widely by radiation oncologists across the country and there are a couple of reasons for that. One is that when we look at the methodology of the studies the surgery was somewhat more extensive than what we typically see for our standard lumpectomy that a surgeon one of our surgeons would do. It was almost an oncoplastic resection. Secondly the pathology analysis was much more specialized. And third, it s a retrospective study. So given those factors it really has not been used widely by most radiation oncologists. There have been a couple of prospective trials that looked at the question can we omit radiation therapy after surgery for DCIS and these looked at wide local excision alone. One of these was done at Harvard and the goal of this trial was to accrue 200 patients but they closed at 158 patients because they met their stopping point. The criteria for this trial was and we ll see this again and again in these DCIS trials where they re trying to omit radiation, low or intermediate grade DCIS, less than or equal to 2.5cm, final margins of 1cm or re-excision without residual DCIS. And in this trial they found that there was a recurrence risk of 2.4% per patient year corresponding to a 5 year rate of 12%. That met their stopping rules and so the trial was stopped

3 MARSHA HALEY, MD 3 at that point and it was felt that even patients in this low risk category would benefit from radiation therapy to reduce the risk of local recurrence. The ECOG 5194 that Dr. Johnson mentioned looked at over 600 patients with the same criteria that I mentioned for the Harvard study. In that study at 7 years the rate was 10.5% for the low to intermediate risk group and 18% for the high risk group. In that study they actually allowed high grade DCIS but only if it was less than 1cm, but at 7 years that recurrence risk was unacceptably high at 18%. Interestingly at 10 years the 2 groups evened out and they were both right around 15%. So again at that point it was felt that radiation was still needed for those low risk patients. A larger study that again Dr. Johnson mentioned was the early breast cancer trial group metaanalysis. They looked at 4 randomized trials at 10 years and they found that the 10 year in breast tumor recurrence with no radiation was 28% versus with radiation at 13%. Interestingly they found that there was greater risk reduction in older women that had radiation and small low grade tumors and negative margins still benefited. Of course there was no effect on cancer specific or other cause mortality. So at that point in time that was let s say at the end of 2014 our conclusions at that time were that radiation therapy after lumpectomy for DCIS significantly decreases the risk of local recurrence both for DCIS and invasive disease, radiation therapy for DCIS does not affect survival. And the question remained are there DCIS cases with low enough risk to omit radiation.

4 MARSHA HALEY, MD 4 So last month this trial came out it was the RTOG 9804, they looked at over 600 patients again it s the same similar criteria; low or intermediate grade DCIS less than or equal to 2.5cm, patients had a segmental mastectomy with surgical margins greater than or equal to 3mm, they were randomized to radiation therapy versus no radiation therapy, Tamoxifen was optional. At 7 years the local failure rate was 0.9% in that radiation arm versus 6.7% in the observation arm. And so looking at this it was felt that at 7 years with a recurrence risk of 6.7% that was a low enough number that we could say that radiation could potentially be omitted in these patients. Interestingly if you look at that recurrence number of 6.7% at 7 years if you look back at the ECOG 5194 there rate at 7 years was 10.5% for that same risk group. And when they look back at this they feel that the reason for that is because only 30% of the ECOG patients received Tamoxifen and twice that many in the RTOG group received Tamoxifen so it s felt that Tamoxifen probably made that difference in the recurrence risk. So in the same issue of Journal of Clinical Oncology there was a grand rounds commentary on ways that radiation oncologists could apply clinical judgement to the results of RTOG Number one was to evaluate the patient s functional status, comorbidities and estimate the long term survival probability. So if the patient had a lot of comorbidities, coronary artery disease, COPD, a life expectancy less than 5 years it wouldn t make sense to radiate for low risk DCIS. Number two was to anticipate the risks of radiation therapy, does the patient have collagen vascular disease such as scleroderma which would increase the risk of radiation therapy side effects significantly. Is the tumor bed in a position where we can t keep the heart rate down to a low level, is the patient morbidly obese where we might have a difficult time sitting the patient

5 MARSHA HALEY, MD 5 up and more risk of side effects. In those cases it might make sense to omit radiation therapy for low risk DCIS. Patient preference should come into account. Some patients really push for radiation despite the low absolute benefit and it s really worth having the discussion with the patient to look at the risk and benefit of radiation. Number four is to look at the type of salvage surgery if the patient recurs. So if the patient has a large breast, a small DCIS it s reasonable to think that if they did recur they could undergo a repeat lumpectomy and radiation at that time. If they had a very small breast it might be that any recurrence required mastectomy so that s a good thing to think about and discuss with the patient beforehand. So our current practice for low risk DCIS we may omit radiation if they meet the RTOG 9804 criteria, however patients with a long life expectancy may have a higher risk of recurrence. So the RTOG 9804 data are only at 7 years. We know from the Early Breast Cancer Meta-Analysis that although the relative risk reduction remains the same, the absolute risk reduction increased over time. So at 5 years the absolute risk reduction was 10%. At 15 years it was 15% and so the concern is as we go out farther with these patients on RTOG 9804 at years we might see an increased risk. So if a patient has a long life expectancy they may have more of a benefit from radiation. And again the risk is likely lower if they re getting endocrine therapy. So if the patient for some reason can t get endocrine therapy if it s contraindicated they might want to think more strongly about radiation.

6 MARSHA HALEY, MD 6 And then for high risk DCIS it s just high grade comedo necrosis large tumor, we still recommend post operative radiation therapy treatment. So our current practice when we re doing whole breast radiation which is the majority of what we do for DCIS if the patient is under 50 years of age we give 50 Gy/25 fractions. And we give a 5-8 fraction boost. If the patient is greater than or equal to 50 years old we can do a hypofractionated course. So the most common one that we use here is Gy/16 fractions plus a 4 fraction boost and that s called the Canadian Fractionation Regimen. An alternative is 40 Gy/15 fractions with no boost which is the England fractionation. And again here in the U.S. if we use hypofractionation we tend to use the Canadian one. With regard to Boosts there s no randomized date for DCIS, we sort of extrapolate from the invasive data which shows a benefit. The retrospective data on Boost is divided so there are four major studies 2 show no benefit, one shows a benefit for everybody and one shows a benefit in certain subgroups so you know it s sort of divided on the Boost. And again there s no randomized data on that. With regard to the hypofractionation all those studies have been done with invasive cancer, however there s one retrospective study from Princess Margaret that showed equivalent outcomes with DCIS, so most of us feel comfortable using the Hypofractionation for DCIS as well. So one of the factors that always comes up is that because DCIS is a non invasive breast cancer it s not life threatening are the risks of radiation outweighing the benefit. And so we do what we

7 MARSHA HALEY, MD 7 can with our techniques to try to minimize the morbidity of radiation. So one thing that we do is CT simulation and 3D planning so we can see the internal anatomy to aim the beams of radiation accordingly to hit the breast and avoid the normal tissue as much as possible. We use mobilization devices. Sometimes we use prone positioning and our goal is to mainly minimize lung dose and minimize heart dose. So on this picture this is a patient that s currently under treatment at Magee, this yellow square is the treatment beam, the orange circle is the tumor bed and then you can see the heart here and this yellow line here is the heart block. So the heart is actually being blocked in this field and you can t see it very well but there s a wire coming around the breast tissue right around here and it shows that we re not blocking breast tissue when we put this in here. So the question has been asked can we just treat part of the breast? Do we need to treat the whole breast for DCIS? The current ASTRO consensus statement is that patients with DCIS are not in the suitable group for APBI. They re in the cautionary group if they have a DCIS less than or equal to 3cm. If the DCIS is greater than 3cm they re considered unsuitable for APBI. One of the biggest studies was done by the American Society of Breast Surgeons and they looked at APBI for DCIS, their local control was 97% at 4 years, similarly there was a phase 2 study that showed a local control of 98% and the Beaumont Outcomes Report that showed a local control of 98%. So in single institution studies it you know meeting strict criteria it does seem to have a pretty good local control rate but the, you know we just don t have long term randomized data to say that it s suitable for every patient with DCIS.

8 MARSHA HALEY, MD 8 So our current clinical practice with DCIS for APBI is to encourage DCIS treatment on clinical study and use a case by case basis for the cautionary group. For post mastectomy radiation for DCIS, it s rarely indicated as Dr. Johnson motioned. The local recurrence risk after mastectomy is less than 2%. A couple studies have looked at this they ve all been retrospective. Beth Israel looked at 211 mastectomies and only there was only a.9% recurrence rate and of those small number all those had close margins. Kaiser did a pathology review their recurrence risk was a little higher it was quite a bit higher it was 7.5% and it was associated with margins less than 2mm and they noticed that patients with younger patients less than 60 years with high grade disease, comedo necrosis, and those close margins may benefit from post mastectomy radiation therapy. And then Harvard did a recent retrospective study and showed that for even for positive margin or close margin the risk is still less than 5% recurrence so their conclusion was even with closer positive margins the recurrence risk was low enough to omit radiation therapy. So in most cases we do omit radiation therapy unless there are grossly positive margins and some of these other high risk factors that they saw in the Kaiser study. So for post presentation question number one, an 80 year old woman with coronary artery disease and COPD has undergone a segmental mastectomy for a 1 cm, grade 1 DCIS, no necrosis

9 MARSHA HALEY, MD 9 and negative margins. She has started endocrine therapy. What is the next step? So I guess we ll raise our hands like we did for other. a) Whole breast radiation therapy b) Observation c) Partial breast radiation therapy Okay so the correct answer is b) observation. Second is a 40 year old woman has undergone a segmental mastectomy for a 2 cm grade 3 DCIS with comedo necrosis, she is planning on taking Tamoxifen, what is the next step? a) Whole breast radiation therapy b) Observation c) Partial breast radiation therapy The correct answer is a) whole breast radiation. And then third is a 75 year old woman has undergone a mastectomy for a 4 cm grade 2 DCIS with a focal positive margin, what is the next step? a) Chest wall radiation b) Re-excision c) Observation So in this case the patient has a focal positive margin, she has a 4 cm tumor it s not high grade, she s 75. We probably would do observation in this patient. Okay any questions?