SAN ANTONIO—A European trial has moved a step closer to answering the question of which radiotherapy technique should be standard for women after breast-conserving surgery for early-stage breast cancer—external-beam whole-breast irradiation or accelerated partial-breast irradiation with brachytherapy.
As reported here at the American Society for Radiation Oncology Annual Meeting, the randomized Phase III GEC-ESTRO trial with 1,184 women showed equivalent five-year local control and survival rates for the two modalities (Abstract LBA 7).
The paper was also published online in The Lancet (doi.org/10.1016/S0140-6736(15)00471-7) immediately after the presentation by Vratislav Strnad, MD, PhD, Professor in the Department of Radiation Oncology at University Hospital Erlangen in Germany.
“This is the first Phase III study proving non-inferiority of APBI in comparison with whole-breast irradiation for selected early-stage breast cancer patients,” he and his colleagues concluded.
In the GEC-ESTRO (Groupe Européen de Curiethérapie of the European Society for Radiotherapy & Oncology) trial, conducted in 16 institutions across Europe, a total of 633 women were randomly selected to receive accelerated partial-breast irradiation with multi-catheter brachytherapy, and 551, to whole-breast radiation with boost.
The study, which was sponsored by the German Cancer Aid (Deutsche Krebshilfe) agency, was conducted from April 2004 to July 2009; patients were age 40 or older with stage 0, I, or IIA tumors.
Whole-breast irradiation consisted of 50 Gy with a boost to the tumor bed of 10 Gy for approximately seven weeks. Accelerated partial-breast irradiation used interstitial multi-catheter brachytherapy for five days.
Median Follow-up of 6.6 Years
After a median follow-up of 6.6 years, the overall rate of local regional recurrence was very low in both study arms: 1.4 percent for accelerated partial-breast irradiation and 0.92 percent for whole-breast irradiation; the rate of second primary breast cancers was 0.49 percent versus 0.75 percent, respectively; and regional recurrence rates were 0.49 and 0.56 percent, respectively.
The researchers concluded that adjuvant accelerated partial-breast irradiation using multi-catheter brachytherapy after breast-conserving surgery in patients with early breast cancer is not inferior to adjuvant whole-breast irradiation with respect to five-year local control, disease-free survival, and overall survival.
The equivalence of local recurrence rates was evident in all age groups and in all tumor types, independent of additional drug therapy including chemotherapy and anti-hormonal therapy, Strnad said.
“The results were not totally surprising, because as we were preparing our Phase III trial, the first long-term results of several smaller Phase II trials were published showing low recurrence rates after breast-conserving treatment and accelerated partial-breast irradiation compared with whole-breast irradiation. What is surprising, however, is how clear the results are.”
A total of 92 percent of patients indicated that they were satisfied with cosmesis after brachytherapy, Strnad reported.
He noted that current guidelines state that patients should be at least age 50 (ESTRO guidelines) or 60 (ASTRO guidelines) in order to receive accelerated partial-breast irradiation.
This study, though, demonstrates excellent results in all participant age groups, including those aged 40 and older, he said.
Corroborates Earlier Findings
The Discussant for the study, which was presented at a plenary session, Julia White, MD, Professor of Radiation Oncology at Ohio State University Comprehensive Cancer Center, said the trial corroborates results of two earlier Phase III trials which reported similar results but were underpowered for their endpoints:
- Researchers at the University of Florence reported a 1.5 percent rate of local recurrence for accelerated partial-breast irradiation versus 1.4 percent for whole-breast irradiation at five years of follow-up (Livi et al: Eur J Ca 2015;4:451-463); and
- The NIO Budapest trial reported local recurrences at 10.2 years of follow-up of 5.5 and 4.6 percent, respectively (Polgar et al: Rad & Onc 2013;108:197-202).
White noted that these three Phase III adjuvant accelerated partial-breast irradiation trials all included similar populations—post-lumpectomy patients with negative margins, almost nearly uniformly over age 50 and ER/PR-positive, tumors less than 1 cm in size, and either grade 1 or 2 tumors.
She said radiation oncologists are very familiar with this study population, which is consistent with the current ASTRO consensus statement for accelerated partial-breast irradiation—which includes tumors less than 2 cm in size, negative margins, positive ER/PR receptors, and being pathologically node negative.
“While the current consensus lists age over 60 years, there is an updated ASTRO consensus statement on accelerated partial-breast irradiation currently under review, which will reduce this age to 50 years,” White said.
She said the study is also confirmation of low-risk pathologic features that are the likely reason for the fewer local recurrences seen in this trial compared with the intraoperative partial-breast irradiation in the ELIOT study (Veronesi et al: Lancet Oncol 2013;14:1269-1277) and TARGIT study (Vaidya et al: Lancet 2014;383:603-613).
GEC-ESTRO reported a 1.9 percent locoregional recurrence rate for partial-breast irradiation, versus 4.4 percent in ELIOT and 3.3 percent in TARGIT, she noted.
Potential Barrier to Adoption
The GEC-ESTRO trial used a complex and technically difficult accelerated partial-breast irradiation method, White said, which is potentially the main barrier to its widespread adoption: “While the 16 institutions in this study successfully completed multi-catheter accelerated partial-breast irradiation, in the U.S. this is the method least often used.”
In addition, White noted that the researchers used a novel accelerated partial-breast irradiation target definition of 2 cm around the tumor including both the surgical and radiotherapy margin, which they previously reported (Strnad et al: Rad & Onc 2015;115:342-348), a target definition that will have to be confirmed in terms of reproducibility.
White pointed to two clear conclusions from this new trial:
- A low-risk population can be identified post-lumpectomy using standard clinical pathologic criteria of nodal stage, tumor size, grade, ER status, and age; and
- Irradiation confined to the high-risk region around the post-lumpectomy cavity yields outcomes that are not inferior to treatment of the entire breast.
“The results of this trial are a large step forward, but caution is still needed,” she said. “The cosmetic outcome for these patients, undeniably an important outcome, is unknown, although it will soon be reported.”
In addition, low-risk breast cancer can have late local recurrences, and there were very few events in this study to determine non-inferiority in that respect.
Finally, “these results cannot be applied to cases with higher-risk clinical pathologic features of the patients you see in your clinic when you go back to work.”
Meanwhile, the optimal delivery method of accelerated partial-breast irradiation continues to evolve: “There are numerous additional Phase III trials that will build on these current findings,” White said, listing the NSABP B-39/RTOG 0413, RAPID OCOG, IMPORT Low MRC, IRMA, and SHARE trials—“These trials will have more than 14,000 women to answer these questions.”