A primary analysis of a multicenter, prospective, single-arm, confirmatory trial of hypofractionated whole breast irradiation after breast-conserving surgery in Japan: JCOG0906

Objective To evaluate the safety of hypofractionated whole breast irradiation in Japanese women after breast-conserving surgery. Methods Japanese women who had invasive breast cancer with a clinical tumor size ≤3 cm, pN0-1c and a negative inked margin were enrolled. Hypofractionated whole breast irradiation (42.56 Gy/16 fractions) was delivered, adding boost irradiation (10.64 Gy/4 fractions) when the surgical margin was ≤5 mm. The treatment course was meant to be completed within 29 days or 33 days (plus boost irradiation). The primary endpoint was the proportion of grade ≥2 of pre-specified late adverse reactions, including telangiectasia, ulceration, fibrosis, fracture, pneumonitis, cardiac ischemia/infarction, pericardial effusion and breast pain, within 3 years. A sample size of 310 patients was set, with one-sided alpha of 0.05, beta of 0.1, threshold value of 8% and expected value of 4%. Secondary endpoints included the proportion of treatment completion within the recommended period and early adverse events within 90 days. Adverse events/adverse reactions were evaluated using CTCAE-3.0. Results Between 2010 and 2012, 312 women were enrolled; 306 received hypofractionated whole breast irradiation, but 6 chose conventional fractionated WBI, with 301 patients (96.5%) treated within the recommended period. Grade 2 early adverse events were found in 38 patients (12.4%); none had grade 3/4. Among the 303 evaluable patients, 13 (4.3%; 90% CI 2.6-6.7) had grade 2/3 late adverse reactions, including one with grade 3 pneumonitis, which was under the threshold value. Conclusion Hypofractionated whole breast irradiation is considered to be safe and one of the standard treatments for Japanese women with margin-negative invasive breast cancer after breast-conserving surgery.