Regional Nodal Irradiation Does Not Extend Breast Cancer Overall Survival

Disease recurrence is reduced in stage I to III breast cancer patients treated with regional nodal plus whole-breast radiotherapy but overall survival is not improved

medwireNews: Two independent studies find no significant overall survival (OS) benefit of adding regional nodal irradiation to post-surgery whole-breast irradiation in early-stage breast cancer patients.

However, both research teams report a favourable effect of regional nodal radiotherapy on disease recurrence in The New England Journal of Medicine.

Between 2000 and 2007, the National Cancer Institute of Canada Clinical Trials Group MA.20 trial accrued a total of 1832 women with stage I to III node-positive or high-risk node-negative disease who had been treated with breast-conserving surgery and adjuvant systemic therapy. Participants were followed up for a median of 9.5 years.

OS was comparable between patients who received whole-breast irradiation with (n=916) and without (n=916) irradiation to the internal mammary, supraclavicular and axillary lymph nodes, with 10-year survival rates of 82.8% and 81.8%, respectively.

But the 10-year disease-free survival rate was significantly improved in the nodal radiotherapy arm compared with the control arm, at 82.0% versus 77.0%. This was also the case for 10-year isolated locoregional and distant disease-free survival rates, at 95.2% versus 92.2% and 86.3% versus 82.4%, respectively.

The incidence of grade 2 or above acute radiation dermatitis (49.5 vs 40.1%) and pneumonitis (1.2 vs 0.2%) was significantly higher in women who did than in those who did not receive nodal irradiation, as was the frequency of delayed lymphoedema (8.4 vs 4.5%), skin problems (6.9 vs 4.3%) and subcutaneous fibrosis (4.1 vs 2.0%).

And although nodal irradiation did not increase rates of cardiac disease and secondary malignancies, it “remains too early” to evaluate the effect of the additional radiotherapy on these conditions, says the team led by Timothy Whelan, from Juravinski Cancer Centre at Hamilton Health Sciences in Ontario, Canada.

Similar results were reported by researcher Philip Poortmans, from Radboud University Medical Center in Nijmegen, the Netherlands, and co-investigators who recruited 4004 women with stage I to III node-positive breast cancer or node-negative disease with central or medial tumours between 1996 and 2004. Approximately three-quarters of participants had undergone breast-conserving surgery, and respectively 99.0% and 66.3% of patients with node-positive and -negative disease had received adjuvant systemic treatment.

After a median follow-up of 10.9 years, the 10-year OS rate was 82.3% for the 2002 patients treated with whole-breast plus internal mammary and medial supraclavicular lymph-node irradiation. This compared with a rate of 80.7% for the 2002 patients who underwent whole-breast irradiation alone, a difference that only approached statistical significance.

But again the nodal irradiation and control groups differed significantly with respect to rates of disease-free and distant disease-free survival, at 72.1% versus 69.1% and 78.0% versus 75.0%, respectively. And 10-year breast-cancer mortality was significantly lower for women in the nodal radiotherapy than the control arm (12.5 vs 14.4%) – a finding in contrast to the MA.20 trial.

Philip Poortmans et al report that “[a]cute side effects of regional nodal irradiation were modest”, with a significant increase in pulmonary fibrosis with the addition of nodal irradiation, at 4.4% versus 1.7%.

They also found “a low rate of heart disease and death from heart disease”, but recommend a longer follow-up to “assess late cardiac complications”.

References

Whelan TJ, Olivotto IA, Parulekar WR, et al. Regional Nodal Irradiation in Early-Stage Breast Cancer. N Engl J Med 2015; 373: 307–316. doi:10.1056/NEJMoa1415340

Poortmans PM, Collette S, Kirkove C, et al. Internal Mammary and Medial Supraclavicular Irradiation in Breast Cancer. N Engl J Med 2015; 373: 317–327. doi:10.1056/NEJMoa1415369

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