J Natl Cancer Inst. 2021 Jul 28:djab113. doi: 10.1093/jnci/djab113. Online ahead of print.
ABSTRACT
BACKGROUND: Uncertainty about the benefit/risk ratio of regional lymph node irradiation led to varying clinical protocols. We investigated long-term late side effects after internal mammary and medial supraclavicular (IM-MS) lymph node irradiation to improve shared decision-making.
METHODS: The multicentre EORTC trial (ClinicalTrials.gov, NCT00002851) randomized stage I-III breast cancer patients with involved axillary nodes and/or a medially located primary tumor. We analyzed late side effects, both longitudinally at every follow-up and cross-sectionally at 5-year intervals. All statistical tests were 2-sided.
RESULTS: Between 1996 and 2004, 46 departments from 13 countries accrued 4004 patients. Median follow-up was 15.7 years. Longitudinal follow-up data showed cumulative incidence rates at 15 years of 2.9% (95% confidence interval [CI] = 2.2%-3.8%) vs. 5.7% (95% CI = 4.7%-6.9%) (P<.001) for lung fibrosis, of 1.1% (95% CI = 0.7%-1.7%) vs. 1.9% (95% CI = 1.3%-2.6%) (P=.07) for cardiac fibrosis, and of 9.4% (95% CI = 8.0%-10.8%) vs. 11.1% (95% CI = 9.6%-12.7%) (P=.04) for any cardiac disease, when treated without or with IM-MS lymph node irradiation. There was no evidence for differences between left- and right-sided breast cancer (Wald chi-square test of treatment by breast side interaction, P=.33 and P=.35, for cardiac fibrosis and for any cardiac disease, respectively). The cumulative incidence probabilities of cross-sectionally reported side effects with a score of 2 or greater at 15 years were 0.1% (95% CI = 0.0%-0.5%) vs. 0.8% (95% CI = 0.4%-1.4%) for pulmonary (P=.02), 1.8% (95% CI = 1.1%-2.8%) vs. 2.6% (95% CI = 1.8%-3.7%) for cardiac (P=.15), and 0.0% (95% CI not evaluated) vs. 0.1% (95% CI = 0.0%-0.4%) for oesophageal (P=.16), respectively. No difference was observed in the incidence of second malignancies, contralateral breast cancer or cardiovascular deaths.
CONCLUSIONS: The incidence of late pulmonary side effects was statistically significantly higher after IM-MS lymph node irradiation, as were some of the cardiac events, without a difference between left- and right-sided treatments. Absolute rates and differences were very low, without increased non-breast cancer related mortality, even before introducing heart-sparing techniques.
PMID:34320651 | DOI:10.1093/jnci/djab113
