Vratislav Strnad, MD, PhD
As reported in The Lancet Oncology by Vratislav Strnad, MD, PhD, of University Hospital Erlangen and Comprehensive Cancer Center Erlangen, Germany, and colleagues, 10-year outcomes in a phase III GEC-ESTRO (Groupe Européen de Curiethérapie and European Society for Radiotherapy and Oncology) trial have shown no significant difference in ipsilateral breast cancer recurrence, disease-free survival, or overall survival with adjuvant accelerated partial-breast irradiation (APBI) using multicatheter brachytherapy vs conventional whole-breast irradiation (WBI) in women with early invasive breast cancer or ductal carcinoma in situ treated with breast-conserving surgery.1 At 5 years, no significant difference in ipsilateral recurrence or survival was observed between APBI and WBI, with APBI being associated with a lower risk of late adverse events.2
Study Details
In the open-label noninferiority trial, 1,328 patients with early breast cancer from sites in the Czech Republic, Germany, Hungary, Poland, Spain, and Switzerland were randomly assigned between April 2004 and July 2009 to receive APBI using multicatheter brachytherapy (n = 655) or WBI (n = 673). WBI was given in 25 daily fractions of 50 Gy over 5 weeks, with a supplemental boost of 10 Gy to the tumor bed. APBI was given at 30.1 Gy (seven fractions) and 32.0 Gy (eight fractions) of high dose–rate brachytherapy in 5 days or as 50 Gy of pulsed dose–rate brachytherapy over 5 treatment days. A total of 633 patients in the APBI group and 551 in the WBI group were eligible for analysis (as-treated population). In the as-treated population, a total of 4% of patients in the WBI group and 6% in the APBI group had ductal carcinoma in situ. The primary endpoint was ipsilateral local recurrence, analyzed in the as-treated population; the noninferiority margin for the recurrence rate difference, defined for 5-year results, was 3 percentage points.
Local Recurrence and Other Outcomes
Median follow-up was 10.4 years (interquartile range = 9.1–11.3 years). Cumulative local recurrence rates at 10 years were 3.5% (95% confidence interval [CI] = 2.0%–5.0%) in the APBI group vs 1.6% (95% CI = 0.4%–2.8%) in the WBI group (difference = 1.93%, 95% CI = –0.018% to 3.87%, P = .074; hazard ratio = 1.88, 95% CI = 0.85–4.12).
For the APBI group vs the WBI group, cumulative rates at 10 years were 1.19% (95% CI = 0.31%–2.06%) vs 0.39% (95% CI = 0.00%–0.94%) for regional (lymph node) metastasis (difference = 0.79%, 95% CI = –0.24% to 1.82%, P = .15), 2.60% (95% CI = 1.30%–3.90%) vs 2.17% (95% CI = 0.90%–3.44%) for distant metastasis (difference = 0.43%, 95% CI = –1.39% to 2.25%, P = .72), and 84.89% (95% CI = 81.97%–87.91%) vs 87.95% (95% CI = 85.10%–90.91%) for disease-free survival (difference = –3.06%, 95% CI = –7.22% to 1.09%, P = .18).
KEY POINTS
- No significant difference in local recurrence at 10 years was observed between APBI with multicatheter brachytherapy vs WBI.
- No significant differences were observed in regional metastasis, distant metastasis, disease-free survival, or overall survival.
The 10-yer cumulative rate of ipsilateral secondary tumors was 2.11% (95% CI = 0.85%–3.37%) in the APBI group vs 1.17% (95% CI = 0.00%–2.10%) in the WBI group (difference = 0.94%, 95% CI = 0.36%–3.49%, P = .21). The cumulative rate of second primary contralateral tumors was 1.56% (95% CI = 0.00%–4.57%) vs 1.18% (95% CI = 0.15%–2.21; difference = 0.38%, 95% CI = –2.80% to 3.56%, P = .45).
Overall survival at 10 years was 90.47% (95% CI = 88.09%–92.91%) in the APBI group vs 89.52% (95% CI = 86.87%–92.25%) in the WBI group (difference = 0.95%, 95% CI = –2.66% to 4.56%, P = .5).
Adverse Events
At 7.5 years, 372 patients in the WBI group and 446 in the APBI group were evaluable for adverse events, with 313 and 375 evaluable at 10 years. The most common toxicity grades at 7.5 years, 10 years, or both were grade 1 in 170 (43%), grade 2 in 64 (16%), and grade 3 in 17 (4%) of 393 patients in the WBI group and grade 1 in 245 (52%), grade 2 in 69 (15%), and grade 3 in 7 (2%) of 375 patients in the APBI group. At 10 years, the most common type of grade 3 adverse event in both treatment groups was fibrosis, occurring in 6 (2%) of 313 patients in the WBI group and 3 (1%) of 375 in the APBI group (P = .56). No grade 4 adverse events were observed in either group. Patients in the APBI group had a significantly lower incidence of treatment-related grade 3 late side effects (1% vs 4%, P = .021). No treatment-related deaths occurred.
The investigators concluded: “Postoperative APBI using multicatheter brachytherapy after breast-conserving surgery in patients with early breast cancer is a valuable alternative to whole-breast irradiation in terms of treatment efficacy and is associated with fewer late side effects.”
DISCLOSURE: The study was funded by German Cancer Aid. For full disclosures of the study authors, visit thelancet.com.
REFERENCES
2. 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 387:229-238, 2016.
