Kate Johnson

May 15, 2012

May 15, 2012 (Barcelona, Spain) — The debate over accelerated partial-breast irradiation (APBI) has a new twist with the 10-year follow-up results from the Hungarian National Institute of Oncology trial, which were presented here at the ESTRO 31: European Society for Radiotherapy and Oncology 2012 Annual Conference.

The randomized phase 3 trial shows that disease control and complications are equivalent in patients receiving APBI and those receiving whole-breast irradiation (WBI). However, APBI has the advantage of treatment brevity and better cosmetic outcome, said Csaba Polgár, MD, PhD, director of the Centre for Radiotherapy at the National Institute of Oncology in Budapest, Hungary.

The results come on the heels of recent concerns about APBI after a retrospective study from the University of Texas M.D. Anderson Cancer Center, in Houston, found a 2-fold increased risk for subsequent mastectomy, as well as postoperative and radiation-related complications, with APBI, compared with WBI, at 5 years (JAMA. 2012;307:1827-1837).

A similar study was presented earlier this month at the American Society of Breast Surgeons 13th Annual Meeting.

In an interview with Medscape Medical News, Dr. Polgár said that the different findings reflect the very different APBI techniques used in Europe and in the United States.

"At least 90% to 95% of the American study population was treated with MammoSite therapy — that is single-channel intracavitary balloon brachytherapy," he said. "We are of the position that this is not a problem for us because in Europe we mainly use multicatheter interstitial brachytherapy."

The study by Dr. Polgár's team was the first randomized study to compare WBI with APBI using multicatheter brachytherapy. It involved 258 patients with early-stage nonlobular breast cancer without extensive intraductal involvement, and resected with negative margins, to either 25 fractions of 50 Gy WBI (n = 130) or APBI (n = 128) delivered to the tumor bed alone, using either interstitial high-dose-rate multicatheter brachytherapy (7 fractions of 5.2 Gy) or electron beams (25 fractions of 50 Gy).

At a median follow-up time of 122.5 months, there were 13 local recurrences (6 in the WBI group and 7 in the APBI group), Dr. Polgár reported. This translates into similar 10-year local recurrence rates for WBI and APBI (5.1% vs 5.9%) and similar 10-year cancer-specific survival rates (94% vs 92%).

In terms of late adverse effects, "we had no grade 3 side effects of the skin from brachytherapy, only 2% grade 3 fibrosis, and only 1 case of necrosis requiring surgical intervention," he said.

In addition, both patient- and physician-rated cosmetic outcomes were "significantly better" for APBI than for WBI, with more patients in the APBI group reporting good to excellent results (81% vs 63%).

Although he did not include mastectomy results in his presentation Dr. Polgár told Medscape Medical News that the rates were similar in both study groups (about 2%). About half of patients with recurrence were treated with mastectomy, and there were no mastectomies because of toxic effects.

The reasons for mastectomy in the American trial are not clear because it was a retrospective analysis, but Dr. Dr. Polgár said the main issue with MammoSite is its toxic effects.

"A few years ago, we projected [the American] result. We warned them," he said. "We used [MammoSite] in a small trial [Radiother Oncol. 2006;79:316-320], and we now have a 64% telangiectasias rate in that population."

But Christine Haie-Meder, MD, chair of the congress and a radiation oncologist at the Institut Gustave Roussy in Villejuif, France, said the technique is also inferior to multicatheter brachytherapy.

"The high local failure rate is linked to the technique used in the United States. With MammoSite, there is one source of irradiation, so you cannot have a good dose distribution. The Europeans did not like this concept. Some Europeans said from the beginning: 'Beware, this is not a good technique, even in terms of cosmetic results, because the dose to the skin is quite high'."

Both Dr. Polgár and Dr. Haie-Meder point to money as the root of the issue.

"It's really a disaster because it was [reimbursed], so a lot of people jumped on this technique without any real assessment of its value, and it became very popular very quickly," said Dr. Haie-Meder.

"As always in the United States, the main issue is with reimbursement," said Dr. Polgár, although he added that there are other important barriers to the use of a multicatheter device with interstitial insertion.

"Of course, some patients would prefer to have only a single catheter. Also, surgeons can implant [the single catheter] and...receive reimbursement; multicatheter brachytherapy is usually done by the radiation oncologist. Treatment planning is also easier for single catheter; you need more skill and expertise to implant the multicatheter device."

Dr. Benjamin Smith

The senior author of the American study, Benjamin Smith, MD, did not attend the conference, but told Medscape Medical News by email that the study "is one of the most important studies to evaluate the concept of partial-breast irradiation because it is a randomized trial with 10 years of follow-up."

"The study supports the notion that appropriately selected patients treated with conventionally fractionated electron-based partial-breast irradiation or accelerated fractionated interstitial brachytherapy can achieve tumor control results comparable to whole-breast irradiation, and toxicity results that may be better than with whole-breast irradiation," continued Dr. Smith, who is from the Department of Radiation Oncology at the M.D. Anderson Cancer Center.

"While this trial validates the concept of partial-breast irradiation, it is very important to note that the target volumes used in this study were substantially larger than the target volumes used by the single-entry balloon- or strut-based catheters most commonly employed in the United States. This important trial from Hungary does not necessarily validate breast brachytherapy as it is typically used in the United States," Dr. Smith said.

He explained that "all of the single-entry catheters used in the United States (MammoSite, MammoSite multilumen, Contura, Savi) are intended to deliver a therapeutic dose of radiation to a 1 cm rim of tissue surrounding the lumpectomy cavity. In contrast, the intention of the interstitial multicatheter technique used by Polgár et al was to deliver a therapeutic dose of radiation to a 2 cm rim of tissue surrounding the lumpectomy cavity. If, as an example, we assume that the lumpectomy cavity was a 5 cm sphere, these differences [mean] that more than twice as much breast tissue receives a therapeutic dose of irradiation with the European multicatheter technique."

He added that the newer generation of single-entry catheters "allow for better sculpting of the radiation dose, which may lead to decreased radiation-related side effects."

Dr. Polgár and Dr. Haie-Meder have disclosed no relevant financial relationships. Dr. Smith's research group receives some research funding from Varian Medical Systems, which makes equipment for both brachytherapy and external-beam irradiation.

ESTRO 31: European Society for Radiotherapy and Oncology 2012 Annual Conference: Abstract OC-087. Presented May 11, 2012.

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