As reported in The Lancet by Vratislav Strnad, MD, of University Hospital Erlangen, Germany, and colleagues, 5-year results of a phase III noninferiority trial showed no difference in local relapse, disease-free survival, or overall survival with adjuvant accelerated partial breast irradiation using multicatheter brachytherapy vs whole-breast irradiation in women with stage 0, I, or IIA breast cancer undergoing breast-conserving treatment.¹ This trial was conducted by the Groupe Européen de Curiethérapie of the European Society for Radiotherapy and Oncology (GEC-ESTRO).

Study Details

In the open-label trial, 1,328 patients with low-risk invasive disease or ductal carcinoma in situ with clear resection margins after lumpectomy at 16 sites in Austria, the Czech Republic, Germany, Hungary, Poland, Spain, and Switzerland were randomized between April 2004 and July 2009 to receive adjuvant accelerated partial-breast irradiation using sole interstitial multicatheter brachytherapy (n = 673) or whole-breast irradiation with 50 Gy and a tumor-bed boost of 10 Gy (n = 655). High-dose–rate brachytherapy consisted of a total dose of 32.0 Gy in 8 fractions or 30.3 Gy in 7 fractions, with fractionation twice a day; pulsed-dose–rate brachytherapy consisted of a total dose of 50 Gy, with pulses of 0.60 to 0.80 Gy/hour at 1 pulse/24 hours a day.

After randomization, 98 patients assigned to whole-breast irradiation and 42 assigned to accelerated partial-breast irradiation either withdrew consent or were excluded due to administrative error; in addition, some patients refused assigned treatment and asked for the alternative treatment after learning the result of randomization. In total, 633 patients in the accelerated partial-breast irradiation group and 551 in the whole-breast irradiation group were included in as-treated analysis. The primary endpoint was local recurrence on as-treated analysis.

Patient and tumor characteristics were similar in the two groups. Patients had a median age of 62 years, 83% were postmenopausal, 95% had invasive carcinoma, and 86% had a primary tumor ≤ 2 cm. Adjuvant treatment included hormone therapy in 87% of patients and chemotherapy in 11%.

Local Recurrence

At a median follow-up of 6.6 years, local recurrence had been observed in 1.44% (95% confidence interval [CI] = 0.51%–2.38%) of the accelerated partial-breast irradiation group vs 0.92% (95% CI = 0.12%–1.73%) of the whole-breast irradiation group (difference = 0.52%, 95% CI = –0.72% to 1.75%, P = .42, within the noninferiority relevance margin of 3%). In a sensitivity analysis, per-protocol analysis among 586 patients who had accelerated partial-breast irradiation and 525 patients who had whole-breast irradiation showed similar results, with 5-year local recurrence of 1.38% vs 0.97% (difference = 0.41%, 95% CI = –0.86% to 1.69%, P = .53).

Additional Efficacy Outcomes

At 5 years, cumulative incidence rates were 0.48% vs 0.18% (difference = 0.30%, P = .39) for regional recurrence, 0.80% vs 0.93% (difference = –0.13%, P = .81) for distant metastases, 0.81% vs 0.96% (difference = –0.15%, P = .81) for second primary contralateral tumors, 4.36% vs 2.47% (difference = 1.89%, P = .778) for second primary tumors at nonbreast sites, and 0.49% vs 0.75% (difference = –0.27%, P = .56) for second primary ipsilateral breast cancers.

Five-year disease-free survival was 95.03% (95% CI = 93.34%–96.75%) with accelerated partial-breast irradiation vs 94.45% (95% CI = 92.54%–96.4%) with whole-breast irradiation (difference = 0.58%, 95% CI = –2.00% to 3.16%, P = .79). Five-year overall survival was 97.27% (95% CI = 96.00%–98.56%) vs 95.55% (95% CI = 93.82%–97.31%; difference = 1.72%, 95% CI = –0.44% to 3.88%, P = .11). There was no difference in breast cancer–related mortality (four deaths in each group, P = .84).

Late Toxicity

The 5-year risk of grade 2 or 3 late skin toxicity was 3.2% with accelerated partial-breast irradiation vs 5.7% with whole-breast irradiation (P = .08). The risk of grade 2 to 3 late subcutaneous tissue side effects was 7.6% vs 6.3% (P = .53). The 5-year risk of grade 3 fibrosis was 0% vs 0.2% (P = .46). No late grade 4 toxicity was observed.

The investigators concluded: “The difference between treatments was below the relevance margin of 3 percentage points. Therefore, adjuvant accelerated partial breast irradiation using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is not inferior to adjuvant whole-breast irradiation with respect to 5-year local control, disease-free survival, and overall survival.”

They continued: “Our trial is the first phase 3 study proving non-inferiority of accelerated partial breast irradiation compared with whole-breast irradiation for selected patients with early-stage breast cancer. Based on our results, accelerated partial breast irradiation using multicatheter brachytherapy can be regarded as a valid alternative treatment option after breast-conserving surgery and can be offered for all low-risk breast cancer patients in clinical routine.” ■

Disclosure: The study was funded by German Cancer Aid. For full disclosures of the study authors, visit www.thelancet.com.

Reference

1. Strnad V, Ott OJ, Hildebrandt G, et al: 5-Year results of accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy versus whole-breast irradiation with boost after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: A randomised, phase 3, non-inferiority trial. Lancet. October 19, 2015 (early release online).