NCIC-CTG MA.20: An intergroup trial of regional nodal irradiation in early breast cancer.

Abstract

LBA1003 Background: Randomized trials have demonstrated that locoregional radiation after mastectomy reduces locoregional recurrence and improves overall survival (OS) in women with node positive breast cancer treated with adjuvant systemic therapy. MA.20 evaluated the addition of regional nodal irradiation (RNI) to whole breast irradiation (WBI) following breast conserving surgery (BCS). Methods: Women with high risk node-negative or node-positive breast cancer treated with BCS and adjuvant chemotherapy and/or endocrine therapy were stratified by positive nodes, axillary nodes removed, chemo- and endocrine therapy and randomized to WBI (50Gy in 25 fractions +/- boost irradiation) or WBI plus RNI (45Gy in 25 fractions) to the internal mammary, supraclavicular, and high axillary lymph nodes. The primary outcome was OS. The Data Safety Monitoring Committee approved the analysis plan for the protocol specified interim analysis of relapse patterns, survival and toxicity at 5 years. Upon review of the data, they recommended release of the results. Results: Between March 2000 to March 2007, 1,832 women were randomly assigned to WBI+RNI (916) or WBI (916). Median follow-up was 62 months. Characteristics of the study population were: mean age, 53.3 years; node negative, 10%; 1-3 positive nodes, 85%; > 4 positive nodes, 5%; adjuvant chemotherapy, 91%; and adjuvant endocrine therapy, 71%. WBI+RNI in comparison to WBI alone was associated with an improvement in isolated locoregional disease free survival (DFS; HR=.59, p=.02, 5 year risk: 96.8% and 94.5% respectively), distant DFS (HR=.64, p=.002, 5 year risk: 92.4% and 87.0% respectively), DFS (HR=.68, p=.003, 5 year risk: 89.7% and 84.0% respectively) and OS (HR=.76, p=.07, 5 year risk: 92.3% and 90.7% respectively). WBI+RNI in comparison to WBI was associated with an increase in grade 2 or greater pneumonitis (1.3% and 0.2% respectively, p=.01), and lymphedema (7.3% and 4.1% respectively, p=.004). Conclusions: The majority of women with node positive breast cancer are now managed by BCS followed by WBI and adjuvant systemic therapy. Results from MA.20 demonstrate that additional RNI reduces the risk of locoregional and distant recurrence, and improves DFS with a trend in improved OS.

The Japanese Breast Cancer Society clinical practice guideline for radiotherapy of breast cancer

“…However, little mature evidence exists regarding this issue for those patients who underwent breast-conserving surgery. Nonetheless, it is established that patients with a considerable number of positive nodes have an increased risk of regional nodal metastasis [19][20][21], and it is reported that regional nodal irradiation improves loco-regional control [20,22,23].…”

“…The MA.20 study reported at ASCO in 2011 is one of the few RCTs investigating regional nodal irradiation for patients after breast-conserving surgery. It shows improvement of a 5-year relapse-free survival rate and overall survival after breast-conserving surgery in patients who underwent elective nodal irradiation that included internal mammary nodes [22]. However, the radiation technique was complicated by adding supraclavicular and internal mammary nodal irradiation to breast tangential irradiation, and they report an increasing incidence of radiation pneumonitis.…”

Postoperative periclavicular radiotherapy in breast cancer patients with 1–3 positive axillary lymph nodes

“…Thus, several authors do not recommend prophylactic irradiation of the periclavicular fossa [17,29,30,34,48]. But according to a recent phase III study with 1,832 patients and 85% with 1-3 pN+, there was a statistically significant decrease in the rate of locoregional failure (LRF) and an increase in DFS for patients with locoregional RT [46]. Yates et al [50] found a significantly lower 10-year survival in case of supraclavicular failure, which is why PCLNI should be considered in this subset of patients.…”

Strahlentherapie

“…Darüber muss individuell entschieden werden [4,5,17,18]. Ergebnisse prospektiver und randomisierter Studien [MRC/EORTC (BIG 2-24) SUPREMO, EORTC-Protocol-22922-10925, EORTC-Protocol-22023-10981(AMAROS), NSABP-B32, NCIC-CTG MA.20; [16,30]] stehen derzeit noch aus.…”