Expert Argues the Case for Whole Breast Irradiation as Standard of Care for Breast Cancer

Lawrence J. Solin, MD, FACR, FASTRO

Lawrence J. Solin, MD, FACR, FASTRO

Physicians opinions vary on whether partial breast irradiation (PBI) should be standard of care in breast cancer, according to a vote taken during the18th AnnualInternational Congress on the Future of Breast Cancer, where physicians did not reach a consensus.

Among the physicians that do not believe PBI should be standard of care was Lawrence J. Solin, MD, FACR, FASTRO. During an educational debate with Bruce G. Haffty, MD, FASTRO, who believes that PBI should be standard of care, Solin commented on relevant data from randomized clinical trials that have shown that PBI may worsen the cosmetic prognosis for patients with breast cancer.

The RAPID trial assessed accelerated PBI for patients with breast cancer using 3-D conformal radiotherapy. The primary endpoint for this study was local recurrence and the secondary endpoints were radiation toxicity and nurse assessed adverse cosmesis. Results showed that although PBI is non-inferior to whole breast irradiation (WBI) in preventing local recurrence, patients who received PBI had a 29% occurrence of adverse cosmesis while only 17% in the WBI arm experienced adverse cosmesis (P<.001) at 3 years. At 5 years, the gap widened with 32% of patients in the PBI arm having shown adverse cosmesis, while only 16% of patients in the WBI arm experienced adverse cosmesis.¹

In the ELIOT trial, a randomized controlled equivalence trial, WBI was compared with the intraoperative radiotherapy technique for partial breast irradiation. At 5 years, the event rate for breast recurrences in the PBI group was 4.4% (range, 2.7%-6.1%) and the event rate in the WBI arm was 0.4% (range, 0.0%-1.0%) (HR, 9.3; 95% CI, 3.3-26.3). Additionally, the WBI arm had a 5-year overall survival rate of 96.9% (95% CI, 95.5%-98.3%) compared with 96.8% (95% CI, 95.3%-98.3%) in the PBI group. These data show no differences between the 2 options; however, this study also showed a larger number of cosmesis cases in the PBI group versus the WBI group.²

Five-year findings from the TARGIT trial, which assessed the potential differences in local control and overall survival in PBI versus WBI, addressed the skin complications seen in previous trials. In the first analysis of overall mortality, at 5 years the rate was 3.9% (95% CI, 2.7%-5.8%) with PBI compared with 5.3% (95% CI 3.9%-7.3%) with whole-breast external beam radiation (P= .099). The 5-year risk for local recurrence in the conserved breast was 3.3% (95% CI, 2.1%-5.1%) with PBI compared with 1.3% (95% CI, 0.7%-2.5%) with WBI (P= .042).³

Reporting on the debate with his peer, Solin explained his stance on WBI in comparison with PBI in breast cancer treatment in an interview withTargeted Oncology. More research is needed to support the idea that PBI can be used for more patients, according to Solin.

TARGETED ONCOLOGY: Why do you believe accelerated PBI should not be the standard of care?

Solin: I'm generally not a great advocate for PBI for 2 reasons. First, in many of the randomized clinical trials, which is the best way to assess a new technology, we're getting signals that the results are worsening with longer trials from maturing randomized trials. That is not an unexpected finding given the large fraction sizes. So, we've gotten signs that PBI may be worse for cosmesis complications and even local control.

[Secondly], in my view, accelerated WBI is a much better alternative and has held up very well in randomized clinical trials with longer-term follow-up. [It's probably a much better alternative for most patients].

TARGETED ONCOLOGY: Can you highlight any research that supports your stance on PBI?

Solin: A number of clinical trials were run with accelerated approaches to try to reduce the treatment times for the [patients' convenience]. They were accelerated whole breast and accelerated PBI trials. If you look at the data, accelerated whole breast has held up very well over time in randomized clinical trials. In contrast, the accelerated PBI is beginning to show signals that it is not as good over time as standard WBI.

Last year in San Antonio, [results from the RAPID trial were reported]. There was some very clear evidence that cosmetic results worsened substantially over time by year 7. The late complication rates were increased in the Canadian RAPID trial in the accelerated PBI arm as well.

[There are 2 other randomized clinical trials that show] slightly worse local control, the ELIOT trial, and the TARGIT-A trial. They're small differences, but there's a slight increase in local recurrence with a PBI.&nbsp;

TARGETED ONCOLOGY: What is the alternative that you believe should be standard of care, and why?

Solin: I think the winner in all this is accelerated whole breast radiation, which is good for many if not most patients. The ASTRO guidelines from 2018 reviewed the data for accelerated WBI, and that basically widened the patient population that is eligible, substantially. Almost all patients are eligible for accelerated whole breast radiation now. So, it's a widely applicable technique, and the results are holding up much better long term.

[During our discussion, Dr Bruce Haffty] raised [several physician] positions on PBI, and when the votes [from the participants] came in, I thought the voting was reasonable. [The voting results] are a good assessment of where we stand with PBI. My view is not that PBI should not be offered to a patient—I would not say that. But I think we have enough information to know [with presentations and some publications] how these treatments are going to perform. The problem is that physicians are trading off a little bit of time and convenience of the patient in exchange for potentially worse cosmetic outcomes and slightly inferior local control. A well-informed patient could make a reasonable judgment about that.

I don't believe it is fair to say these are equivalent techniques. But I don't think it's inappropriate to offer a patient PBI and let the patient make the tradeoff. A lot of the patients I [treat] choose to take a slightly longer treatment course in exchange for slightly better outcomes over time.

References

1. Whelan T, Julian J, Levine M, et al. RAPID: A randomized trial of accelerated partial breast irradiation using 3-dimensional conformal radiotherapy (3D-CRT).Cancer Res. 2019;79(suppl 4; abstr GS4-03). doi: 10.1158/1538-7445.SABCS18-GS4-03.
2. Vaidya JS, Wenz F, Bulsara M, et al. Risk-adapted targeted intraoperative radiotherapy versus whole-breast radiotherapy for breast cancer: 5-year results for local control and overall survival from the TARGIT-A randomised trial.Lancet. 2014;383(9917):603-613. doi: 10.1016/S0140-6736(13)61950-9.
3. Veronesi U, Orecchia R, Maisonneuve P, et al. Intraoperative radiotherapy versus external radiotherapy for early breast cancer (ELIOT): a randomised controlled equivalence trial.Lancet Oncol. 2013;14(13):1269-1277. doi: 10.1016/S1470-2045(13)70497-2.