Penny R. Anderson, MD

This randomized trial by Vicini and colleagues is extremely important and could lead to a major shift in the current paradigm of radiation treatment for patients with high-risk, early-stage breast cancer receiving adjuvant radiation therapy.

Demonstrating that the boost can be safely and effectively delivered concurrently with hypofractionated whole-breast radiation therapy gives patients the option of completing their course of radiation in essentially half the overall treatment time without jeopardizing efficacy. This is extremely important as patients face the many challenges of traveling to their daily radiation treatments.

The results of this trial also provide high-quality randomized data for clinicians to share with patients to help ease the burden of their breast cancer radiation treatments.

Lori J. Pierce, MD, FASTRO, FASCO

The RTOG 1005 was activated in 2011 — where were we as the radiation oncology community with respect to treatment for breast cancer in 2011? We were witnessing the adoption of hypofractionated whole-breast irradiation in this country, but adoption was slow and there are many reasons why the adoption was so modest. Clearly, one of the issues for those using hypofractionated radiotherapy was the uncertainty of adding a boost. There were few data to define the indications for and the toxicity of a tumor bed boost in patients treated with hypofractionated whole-breast irradiation. When a tumor bed boost was indicated, there was lack of consensus regarding the appropriateness of hypofractionated whole-breast irradiation. There were practical reasons for whether and how to incorporate a boost that held some people back from using hypofractionated whole-breast irradiation. Even with some of the original trials of hypofractionation, there were patients who received a boost, but there was no systematic analysis of the impact of a boost, specifically on long-term cosmesis.

We were very fortunate to have the MD Anderson clinical trial of conventional radiation therapy vs. hypofractionated whole-breast irradiation, where all patients received a sequential boost in that study.

The question then became: Can we use a concomitant boost while giving whole-breast irradiation? To my knowledge, three clinical trials are looking at this. The first, presented at ASTRO in 2021, had two experimental arms with a concurrent boost, and the arm that went to 48 Gy was proven to be noninferior with respect to ipsilateral breast tumor recurrence. When looking at moderate to marked adverse events, they were low in all arms of the trial, and this included breast shrinkage and differences in the appearance of the breast.

There is another trial out of Germany that we’ll hear reported on relatively soon.

We then have NRG/RTOG 1005, which was presented so well by Dr. Vicini. No differences were observed in recurrence at 5 and 7 years between patients who had a sequential boost vs. those who had a concurrent boost.

It was interesting that the HR had to be less than 2.12 to be defined as noninferior, but it has to do with the fact that the absolute recurrence rates were so low. Although we saw that the curves slightly increased over time, it will be very unlikely that we will see a clinically relevant increase over time.

The authors are absolutely to be congratulated. This was the first randomized breast cancer trial with specific dose volume constraints for 3D or inversely planned intensity-modulated radiation therapy. The researchers obtained patient quality assessment and physician assessment of cosmesis, which is very important because this trial had no restrictions on breast size, separation or use of chemotherapy.

Should a concurrent dose with hypofractionated whole-breast irradiation be incorporated into treatment options for early-stage breast cancer? Absolutely. This was the right trial at the right time. It helped to encourage the use of hypofractionation to the whole breast at a time when uptake was modest. We have now seen very low rates of ipsilateral breast tumor recurrence with concurrent tumor bed boost. We saw high rates of good to excellent cosmesis and it clearly set the bar for the ability to use dose volume-planning constraints in national trials. However, it is critical that we utilize contemporary dose-planning constraints. There is no need to use techniques that might increase the interval dose to treat patients with a concurrent boost.

Thanks to RTOG 1005, we now have more tools in our toolbox so we can effectively treat patients with early-stage breast cancer, continue to individualize the treatments for breast cancer and also maximize convenience for patients. With the caveats for concurrent boost that we use contemporary dose-planning constraints and approaches that are similar to how we would plan a sequential boost so that we don’t have an increase in interval dose, I would argue that this is the preferred approach for patients undergoing whole-breast moderate dose hypofractionation as opposed to a sequential tumor bed boost.

Finally, as a reminder to us all, the projected accrual of minorities for this study was based upon the approval of NSABP B 39. Only 2.5% of patients in the study were Hispanic/Latino, and only 6% were Black. These percentages are much lower than the percentages in our U.S. population. As a reminder to us all, we need to take the time to actively and equitably recruit patients onto clinical trials so that all patients with cancer have equal access to the highest-quality cancer care.