As reported in The Lancet by Chua et al, the phase III BIG 3-07/TROG 07.01 trial has shown reduced risk of local recurrence with vs without tumor bed boost after conventional or hypofractionated whole-breast irradiation (WBI) in women receiving breast-conserving surgery for non–low-risk ductal carcinoma in situ (DCIS). No difference between conventional vs hypofractionated WBI was observed.
Study Details
The open-label trial included 1,608 patients with at least 1 mm of clear radial resection margins after breast-conserving surgery from seven countries in Europe, Australia, New Zealand, Singapore, and Canada. They were randomly assigned between June 2007 and June 2014 to receive WBI with tumor bed boost (n = 803) or no boost (n = 805). A total of 503 patients (category A) were randomly assigned to one of four groups (1:1:1:1) with boost vs no boost after conventional vs hypofractionated WBI. The remaining patients underwent random assignment to boost vs no boost after the involved study centers prespecified use of conventional or hypofractionated WBI. In total, 831 patients received conventional WBI and 777 received hypofractionated WBI. Conventional WBI consisted of 50 Gy in 25 fractions and hypofractionated WBI consisted of 42.5 Gy in 16 fractions. The boost dose was 16 Gy in 8 fractions. The primary endpoint was time to local recurrence.
Local Recurrence
In patients with resected non–low-risk DCIS, a tumor bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomized trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalizability of the results.— Chua et al
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Median follow-up was 6.6 years. Among all patients, the 5-year rate of freedom from local recurrence was 97.1% (95% confidence interval [CI] = 95.6%–98.1%) in the boost group vs 92.7% (95% CI = 90.6%–94.4%) in the no-boost group (hazard ratio [HR] = 0.47, 95% CI = 0.31–0.72, P < .001).
No significant differences in 5-year rates of freedom from local recurrence were observed between conventional vs hypofractionated WBI in the category A group (94.4% vs 93.7%; HR = 0.94, 95% CI = 0.51–1.73, P = .84) or among all randomly assigned patients (94.9% vs 94.9%; HR = 0.94, 95% CI = 0.51–1.74, P = .85); the interaction between tumor bed boost and WBI fractionation was not significant in category A (P = .89) or among all patients (P = .89).
The 5-year rate of freedom from any disease recurrence was 93.7% in the boost group vs 89.6% in the no-boost group (HR = 0.63, 95% CI = 0.46–0.87, P = .0042). No significant differences were observed for conventional vs hypofractionated WBI. Overall survival at 5 years was 99.0% in the boost group vs 98.2% in the no-boost group (HR = 0.81, 95% CI = 0.45–1.45, P = .47).
Adverse Events
Any-grade acute adverse events occurred in 58% of patients in the boost group vs 43% of the no-boost group (grade 3 in 45 vs 23 patients, grade 4 in 2 vs 0 patients). Any-grade late adverse events occurred in 35% vs 24% (grade 3 in 36 vs 32 patients, grade 4 in 5 vs 2 patients). The boost group had higher rates of grade ≥ 2 breast pain (14% vs 10%, P = .003) and induration (14% vs 6%, P < .001). No significant increase in risk of radiation pneumonitis, cardiac disease, or radiation-related second malignancy was observed in the boost group.
The investigators concluded, “In patients with resected non–low-risk DCIS, a tumor bed boost after WBI reduced local recurrence with an increase in grade 2 or greater toxicity. The results provide the first randomized trial data to support the use of boost radiation after postoperative WBI in these patients to improve local control. The international scale of the study supports the generalizability of the results.”
Boon H. Chua, MBBS, of Nelune Comprehensive Cancer Centre, Prince of Wales Hospital, Randwick, Australia, is the corresponding author for The Lancet article.
Disclosure: The study was funded by the National Health and Medical Research Council of Australia, Susan G. Komen for the Cure, Breast Cancer Now, OncoSuisse, Dutch Cancer Society, and Canadian Cancer Trials Group. For full disclosures of the study authors, visit thelancet.com.
