Nadim Nasr, MD

On August 4, the American Society of Radiation Oncology (ASTRO) published evidence-based guidelines for the use of hypofractionated whole breast irradiation (WBI). As a result, U.S. cancer centers now have an official position from ASTRO regarding the treatment protocols that have been in use for years in Canada, the United Kingdom and Australia.

However, some controversy remains regarding the suitability of the accelerated treatment schedule, particularly given what many view as insufficient follow-up on long-term complications. Radiation oncologist Nadim Nasr, M.D. discusses his views on the guidelines and the potential impact hypofractionation will have on the breast cancer treatment paradigm.

What is your opinion about the use of hypofractionated WBI in treating early-stage breast cancer?

Given the current data that is available, I think it shows promise – but it still requires follow-up. Hypofractionation could have widespread implications for breast cancer treatment, both in the United States and around the world. If this treatment schedule is found to be equivalent in local control, survival, cosmesis and long-term complications when compared to conventional fractionation, it will have a very significant impact.

Unfortunately, in order to sufficiently demonstrate these end points, you need very long follow up, preferably around 15 years. If you look at the data from conventional fractionation, we didn’t really start to see the long-term morbidity or mortality – primarily from cardiovascular disease – until 10-15 years after treatment. With hypofractionation, there is a particular concern that there will be an increase in late complications because you are delivering larger doses per fraction.

We now have four high-quality randomized trials that have shown hypofractionation was not inferior to standard radiation in selected women, with the longest follow-up at 10 years for the Canadian trial. However, long-term data on lung and cardiac morbidity from the randomized trials has really not emerged yet. Also, there are some very significant groups of breast cancer patients in which the suitability of hypofractionation has not been addressed, i.e. patients with DCIS; under the age 50; and those requiring a boost to their lumpectomy cavity, chemotherapy or lymph node radiation. So there is promise, but we still have a long way to go.

What are your thoughts on the recently issued ASTRO guidelines?

I feel the guidelines are valuable in that they summarize the salient points of the four randomized trials, while also highlighting their shortcomings as well as the areas that need further evaluation. The task force was able to use these trials to delineate clinically useful, evidence-based guidelines on whole breast hypofractionation. Most importantly for radiation oncologists, they were able to define a population of patients that is suitable for the accelerated treatment.

How does hypofractionation compare to APBI?

These two types of radiation therapy are not mutually exclusive and there is a large population of breast cancer patients for whom either of these treatments are an option. However, at this point in time I believe the benefits of APBI outweigh the benefits of a hypofractionated treatment schedule. At Virginia Hospital Center, we feel that APBI in properly selected patients is a highly effective treatment option. Compared to hypofractionation, APBI provides better control over the dose delivery, treats a lower volume of tissue and enables patients to complete treatment in even less time.

However, there are obviously certain patients who, mostly due to anatomic constraints like limited distance between the skin or chest wall, are not adequate candidates for APBI but still want a shorter course of treatment. As long as these patients meet the current criteria for hypofractionation, I think it is a suitable treatment option.

Do you offer hypofractionation at Virginia Hospital Center? If so, what patient selection criteria do you follow?

We certainly do practice hypofractionation on selected patients. For patients that are eligible for breast conservation therapy, we take each case individually and use certain factors to determine if they are better suited for APBI, conventional whole breast or hypofractionation. Our current treatment paradigm is that if a patient is a candidate for APBI, that is what we recommend. Hypofractionation is only offered if a patient wants a shorter treatment but doesn’t qualify for APBI.

If we use hypofractionation at Virginia Hospital Center, the main patients that are suitable are 50 years of age or older with right sided disease; have a confirmed pathology stage of T1 or T2 with no nodal involvement; do not require systemic chemotherapy; and whose anatomy allows for proper radiation treatment planning. However, only a very small percentage of cases end up receiving hypofractionation because a majority are eligible for APBI.

What is your opinion about a tumor-bed radiation boost in hypfractionation?

This is one area where the ASTRO guidelines task force was unable to reach a consensus. The guidelines say that if a patient is felt to require a tumor bed boost, it is not appropriate to use hypofractionation alone. However, when a boost is indicated, there is no consensus among the task force members as to the optimal dose schedule for hypofractionation or the boost itself.

The current evidence we have about a tumor-bed boost doesn’t provide much guidance, either. There are mainly two historic trials that study the effects of a boost – these examined a boost combined with conventional fractionation for patients with a high risk of local failure, i.e. closer positive margins or poor differentiation. These studies showed a small, modest improvement in local control, but also a slightly worse cosmetic outcome. And the largest benefit was in patients who were younger than 40, which is a group of patients who aren’t eligible for hypofractionation anyway, based on the ASTRO guidelines.

It’s very much up in air about when and how to use a tumor-bed boost of radiation. Based on the lack of current guidance, if a patient at Virginia Hospital Center requires a boost, we will offer them APBI or conventional fractionation, but not hypofractionation.

Looking forward, how will hypofractionation fit into the spectrum of radiation therapy options for breast conservation therapy?

The women who are going to benefit the most are those for whom a standard course of treatment is the most burdensome – mainly those who have to travel long distances or who might otherwise choose a mastectomy over BCT simply because of the inconvenience of the radiation treatment.

I think hypofractionation could have a big impact on the breast cancer treatment paradigm, as we accumulate more evidence. We need to demonstrate that it offers not only the same outcomes in terms of local control, but also the same long-term complication risks.

Dr. Nasr is a board-certified radiation oncologist at Virginia Hospital Center in Arlington, Virginia.