Nick Mulcahy

November 09, 2012

BOSTON, Massachusetts — For some women with early breast cancer, the convenience of accelerated partial-breast irradiation (APBI) comes at a cost — a poorer cosmetic outcome, according to a major international randomized clinical trial.

The APBI used in the study was 3D external-beam radiation therapy (3D-CRT).

The study is ongoing, but at 3 years, 32% of the women with early breast cancer treated with APBI had an "adverse cosmetic outcome," compared with 19% of women treated with whole-breast irradiation (WBI) (P < .0001); the appearance of the breast was evaluated by trained study nurses. All of the participants undergone a lumpectomy.

The interim results of the phase 3 trial, known as RAPID (Randomized Trial of Accelerated Partial Breast Irradiation Using 3D Conformal External Beam Radiation Therapy), were presented here at the American Society for Radiation Oncology 54th Annual Meeting.

Radiation can cause fibrosis or thickening of breast tissue and can adversely affect cosmetic results, explained lead author Timothy J. Whelan, MD, from Juravinski Cancer Centre in Hamilton, Ontario, Canada, during a meeting press conference.

The short time between fractions with APBI is one possible explanation for its increased toxicity and the related adverse cosmetic effects, he said.

Cosmetic outcome is a secondary outcome in the study but is a significant one, he told Medscape Medical News.

 
Cosmetic outcomes are very important. Dr. Timothy Whelan
 

"Cosmetic outcomes are very important because breast-conserving therapy was created to preserve the breasts," Dr. Whelan explained. There are aesthetic and emotional dimensions to the preservation, he added.

The results are "very solid" and provide "high-level evidence," said Bruce Haffty, MD, from the Cancer Institute of New Jersey and the Robert Wood Johnson Medical School in New Brunswick, who acted as discussant for the trial.

"These are the most objective, robust data that we have seen," Dr. Haffty said. Mixed results have come from a number of phase 2 trials that looked at toxic effects from APBI and WBI, but they were inferior studies, he told meeting attendees.

"We are pushing the envelope of the normal toxicity curve," he said about the study's APBI schedule, which consisted of 38.5 Gy in 10 fractions twice daily. In contrast, the WBI consisted of 50 Gy in 25 fractions or 42.5 Gy in 16 fractions once daily.

Dr. Whelan pointed out that WBI has been proven to reduce local recurrence, prevent mastectomy, and improve overall survival, but it is not used in up to 30% of women, in part because of "inconvenience." APBI was developed to speed up the delivery of treatment. "Women have a lot of interest in getting shorter radiation treatments," he said.

Although all of the women in the trial had the option of receiving extra boost irradiation, it was used infrequently in the WBI group. This is another possible explanation for the difference in cosmesis between the 2 methods, said Dr. Whelan.

 
The results are not necessarily applicable to interstitial or balloon-based therapy. Dr. Bruce Haffty
 

 

Dr. Haffty was quick to clarify that the study results are limited to 3D CRT. "The results are not necessarily applicable to interstitial or balloon-based therapy, which typically radiate a lower volume of breast tissue," he said.

Patients and Oncologists Also Rated Appearance

The 2135 study participants, from 33 centers in Australia, Canada, and New Zealand, were at least 40 years of age. They had either invasive breast cancer or ductal carcinoma in situ less than 3 cm in size, and were treated with lumpectomy from February 2006 to July 2011. The women were lymph node negative.

The primary study outcome is the rate of ipsilateral breast tumor recurrence, but data are not mature enough for interim results to be reported, said Dr. Whelan.

Adverse cosmetic outcome (a fair or poor rating, as opposed to an excellent or good rating) was assessed by a trained study nurse at baseline and 3 and 5 years after treatment.

At baseline (n = 1995 participants), 17% of the WBI patients and 19% of the APBI had an adverse cosmetic outcome (P = .35).

At 3 years (n = 850 participants), the adverse outcome remained fairly steady in the WBI patients (19%); however, adverse cosmesis had "deteriorated" in the APBI patients (32%), Dr. Haffty observed.

In addition to the nurses, cosmetic outcome was evaluated by 2 more assessors: the patients themselves and a panel of radiation oncologists who reviewed unlabeled digital photographs.

Both rated APBI results worse. The patients found that adverse cosmesis was significantly worse in the APBI group than in the WBI group at 3 years (26.2% vs 18.4%; P = .004), as did the radiation oncologists (35.1% vs 16.6%; P < .0001).

Radiation toxicity is one of the other secondary study outcomes. Dr. Whelan indicated that most of the toxic effects in both groups were moderate.

Grade 1 and 2 late radiation toxicities, such as breast induration, were higher with APBI (53.0% and 12.0%, respectively) than with WBI (43.0% and 3.4%, respectively). Grade 3 and 4 toxicities were rare in both groups.

"Our study...found that APBI using 3D external-beam radiation therapy can increase the risk of moderate radiation side effects, which may affect cosmetic outcome for some patients. 3D CRT APBI treatment needs additional research," said Dr. Whelan in a press statement.

The study was sponsored by the Ontario Clinical Oncology Group, the Canadian Institutes of Health Research, and the Canadian Breast Cancer Research Alliance. The study authors have disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 54th Annual Meeting: Abstract 30. Presented October 28, 2012.

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