Zosia Chustecka

October 21, 2015

SAN ANTONIO ― The results are clear from the latest trial of accelerated partial-breast irradiation (APBI), which used multicathether brachytherapy. Women with early-stage breast cancer treated with this APBI technique did equally well as those who received whole-breast irradiation (WBI), with no difference in the rates of local recurrence, disease-free survival, and overall survival at 5 years.

Now there is proof that APBI is not inferior to WBI for breast cancer, and this represents a paradigm shift, Frank Vicini, MD, from 21st Century Oncology of Michigan, commented to Medscape Medical News. This ABPI technique involves radiotherapy for a much shorter period, only 4 to 5 days, compared with 5 weeks with WBI, he said. This trial proved the scientific principle with level 1 evidence, but it applies only to this technique, he pointed out.

Dr Vicini was not involved in the latest trial, but he is heading a huge, ongoing national study, known as B-39/RTOG 0413, that is comparing various types of ABPI with WBI in more than 4000 women.

There are numerous types of ABPI, Dr Vicini explained. Results of previous trials that have used an intraoperative radiotherapy device (the TARGIT and ELLIOT trials) have been negative ― there was significantly more local recurrence, he noted.

The latest trial, presented here at the American Society for Radiation Oncology (ASTRO) 57th Annual Meeting and published online simultaneousy in the Lancet, used multicatheter brachytherapy to deliver the radiation directly to the tumor bed. This involved implanting very thin, wirelike pins through the skin (often through scar tissue) under CT guidance, explained lead author Vratislav Strnad, MD, professor of radiation oncology at the University Hospital Erlangen in Germany. For the procedure, women could receive light, general anethesia or local anesthesia. When the pins were removed after the radiotherapy, they left no noticeable marks on the skin, he told Medscape Medical News.

The women in this ABPI group received radiotherapy twice daily for 4 to 5 days postoperatively (either 32 Gy in eight fractions or 30.3 Gy in seven fractions); the women in the WBI group received radiotherapy daily for 5 weeks (total dose, 50-50.4 GY, delivered in 25 to 28 fractions).

The trial was conducted in 1184 patients with low-risk invasive breast cancer (stages 0, I, and IIA) and ductal carcinoma in situ after they had undergone breast-conserving surgery. Median follow-up was 6.6 years.

Dr Strnad and colleagues reported that there were no differences in outcomes between the two groups.

Table.

  ABPI WBI
5-Year local recurrence rates 1.40% 0.90%
5-Year disease-free survival 95.00% 94.50%
5-Year overall survival 97.30% 95.60%

 

In terms of adverse events, the women who received the ABPI appeared to fare better. The 5-year risk for grade 2-3 late side effects to the skin was 3.2% with APBI vs 5.7% with WBI (P = .08), and 5-year risk for grade 2-3 subcutaneous tissue late side effects was 7.6% vs 6.3% (P = .53). The risk for severe (grade 3) fibrosis at 5 years was 0.2% with WBI and 0% with APBI (P = .46).

"The results of our study show that at present, multicatheter brachytherapy is an attractive and viable APBI treatment option for low-risk breast cancer patients after breast-conserving surgery," Dr Strnad said in a statement.

"The results were not totally surprising, because as we were preparing our phase 3 trial, the first long-term results of several smaller phase 2 trials were published showing low recurrence rates after breast-conserving treatment and APBI in comparison to WBI. What is surprising, however, is how clear the results are. Our favorable results are in contrast with the disappointing and controversial results reported from other studies that used other APBI techniques, such as intraoperative and external-beam radiation therapy," he said.

At the meeting, Dr Strnad told the audience that multicatheter brachytherapy offers a viable alternative to WBI and can be offered to all women with low-risk breast cancer.

However, the technique that was used in this trial is "the most complex method" for delivering APBI, and it is the least commonly used method in the United States, pointed out discussant of the article Julia White, MD, professor of radiation oncology at the Ohio State University, in Columbus. She said that this is the largest phase 3 trial of ABPI vs WBI reported so far and that this is a large step forward, but she also urged caution, because these results cannot be applied to women with higher-risk breast cancer.

Approached for comment on the study, Aphonse Taghian, MD, PhD, professor of radiation oncology at the Massachusetts General Hospital Cancer Center, in Boston, said the technique used in this study requires expertise, in that the catheters need to be inserted into exactly the right spot, and there is a learning curve with this. He told Medscape Medical News that he has tried various interstitial implantation devices for delivery of ABPI, but has now dropped that approach: "It didn't work for me." He now uses external-beam 3D conformal radiotherapy, which is noninvasive, and says that this is the most widely used form of ABPI in the United States. In the ongoing B-39 trial, the choice of ABPI is left to the investigator, and about 70% of the centers involved in that trial are using external beam, which probably reflects national use, he said. Only about 6% of centers are using interstitial brachytherapy, and the remainder are using intercavity devices, such as balloon catheter.

In a Lancet editorial that accompanies the published trial, the authors, Charlotte Coles, MD, consultant clinical oncologist at Addenbrookes Hospital, Cambridge, United Kingdom, and John R. Yarnold, MD, consultant clinical oncologist at the Academic Radiotherapy Unit at the Royal Marsden Hospital, London, say it is "a welcome relief to comment on a carefully designed and conducted trial, presented and discussed in a measured fashion." They also agree with the authors on the importance of waiting for 10-year results from this trial.

So does this trial "herald the death knell for whole-breast irradiation, with APBI becoming the new standard?" they ask. "We think not."

This trial presents maturing data, but further evidence is required from the five ongoing or as yet unreported trials with ABPI, which in total involve some 14,000 patients, they write.

"We know that breast cancer represents a spectrum of different diseases," the editorialists comment, and "radiotherapy is no longer a one-size-fits-all strategy but ranges from highly complex treatments to the breast and regional lymph nodes, to complete avoidance of any radiation.

"It is likely that APBI will have a place within this array of treatments," they comment. "The challenge will be to select the most appropriate treatment for the individual patient and to personalise radiotherapy based on tumour biology."

Funding for this trial came from the German Cancer Agency. Dr Strnad reports receiving consultation fees from Nucletron Operations BV, an Elekta Company, outside the submitted work. All other authors, Dr Coles, and Dr Yarnold have disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 57th Annual Meeting: Abstract LBA7. Presented October 19, 2015.

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