The background to the trial is that nearly three decades ago two trials were published from the Danish and Canadian groups that showed that if you added comprehensive local regional irradiation to systemic therapy, both in pre- and postmenopausal patients at intermediate and high risk of recurrence, the 10-year overall survival was improved by around 10%. But there were concerns about the quality assurance of these trials. Firstly, the systemic therapy with cyclophosphamide, methotrexate and 5FU was considered to be suboptimal. The local regional recurrence rates in the Danish trial in the non-irradiated group at ten years were relatively high at 30%, much higher than we’d see in contemporary North American series.

So what we wanted to do was to repeat the trial in intermediate-risk cancer with 1-3 positive nodes and who are node negative with other risk factors and treat them with radiotherapy, surgery and contemporary systemic therapy to assess the impact on 10-year overall survival.

What was the study design?

The study design was a randomised trial where the target was the chest wall because that’s where most of the local recurrences occur. Patients were allowed to treat the internal mammary nodes but the randomisation was to chest wall irradiation or to no chest wall irradiation with the primary endpoint at ten years.

What were the key results?

For the primary endpoint of the trial at ten years in 1,607 patients, which was the intention to treat population, there was no difference in overall survival at ten years.

What is the clinical significance of these results?

The primary significance is that we should consider omission of chest wall irradiation in patients who meet the eligibility criteria of the trial, that’s 1-3 positive nodes or node negative with other risk factors. There was a small impact on local recurrence from chest wall irradiation and although the relative risk of [??] on the chest wall was reduced by nearly over 50%, the absolute difference was very small, less than 2% and we don’t think that’s clinically significant.