Sweet 15.

Top Line: What long-term toxicities are seen after regional nodal irradiation for breast cancer?

The Study: The EORTC 22922 trial randomized >4000 women with positive axillary nodes or central/medial primary tumors to +/- regional nodal irradiation (RNI). At 15 years, RNI reduced breast cancer recurrence 27.1 → 24.5% and breast cancer mortality 19.8 → 16%, but there were no differences in OS, DFS, or DMFS. Without the OS benefit, the decision to add RNI comes down to risks and benefits. We’ve seen the 15 year benefits, and here are the 15 year risks. At 15 years, RNI increased the cumulative incidence of lung fibrosis (2.9 → 5.7%). The majority of these events were asymptomatic, but a small but significantly higher proportion of RNI patients had symptomatic lung fibrosis (0.1% → 0.8%). There was also an increase in the 15-year rate of any cardiac disease with RNI (9.4 → 11.1%). Interestingly, there was no difference in cardiac disease between left vs right sided cases. Second cancers developed in 14.6% of patients (6.6% contralateral breast cancer), but there was no increase in the risk of second cancer with RNI. With respect to mortality, the only difference between arms was the reduction in breast cancer mortality with RNI. There was no difference in cardiac mortality or non-breast cancer mortality. The long-term treatment outcomes and long-term toxicity still leave plenty of room for debate. But what we can see is that, in a very broad group of breast cancer patients, RNI reduces recurrence risk and breast cancer mortality with a small increase in pulmonary fibrosis and cardiac disease but no increase in non-cancer mortality or second malignancy risk. Furthermore, these risks are likely lower than the historically perceived risks of RNI for breast cancer.

TBL: Your decision to use RNI for breast cancer is now informed by 15 year treatment and toxicity outcomes from EORTC 22922. | Poortmans, J Natl Cancer Inst 2021