Long-term follow-up suggests postoperative internal mammary and medial supraclavicular irradiation reduces the risk of recurrence and disease-specific but not all-cause mortality
Fifteen-year findings from a phase III trial indicate that the benefits of internal mammary and medial supraclavicular (IM-MS) irradiation after breast cancer surgery do not translate into a gain in overall survival (OS).
The EORTC 22922/10925 study included patients aged 75 years or younger who underwent mastectomy or breast-conserving surgery plus axillary staging for stage I–III, axillary lymph node-positive breast cancer, or central or medially located primary disease, the trial investigators explain in The Lancet Oncology.
After a median 15.7 years of follow-up, the primary endpoint of 15-year rate of OS did not differ significantly between the 2002 patients who were randomly assigned to receive 50 Gy over 25 fractions of radiation and the 2002 patients who did not receive IM-MS radiotherapy, at 73.1% versus 70.9%.
Receipt of IM-MS radiotherapy was associated with a significant reduction in the 15-year rate of breast cancer recurrence compared with no radiation (24.5 vs 27.1%, hazard ratio [HR]=0.87), as well as breast cancer-specific mortality (16.0 vs 19.8%, HR=0.81).
But differences between the IM-MS and control groups did not reach statistical significance for the 15-year rates of disease-free survival (60.8 vs 59.9%) and distant metastasis-free survival (70.0 vs 68.2%), say Philip Poortmans, from the University of Antwerp in Belgium, and co-authors.
They believe that the lack of OS benefit may be because the “trial was underpowered to detect small absolute differences, as outcomes were much better than anticipated following inclusion of a relatively favourable patient group” when compared with earlier trials.
“However, the significant reduction of breast cancer mortality and breast cancer recurrence demonstrates that a benefit exists with IM-MS irradiation for at least a subgroup of patients, which might be, however, at least partially offset by an increase in late non-breast cancer-related mortality”, the investigators observe.
Analysis of late adverse events in the IM-MS radiotherapy and control groups at 15 years showed that cardiac fibrosis occurred in 2.0% versus 1.1%, with cardiac disease in 8.6% versus 7.2%, and cardiac mortality in 1.4% of both arms.
Charlotte Coles, from the University of Cambridge in the UK, and co-authors of an accompanying comment write that “we might feel reassured by the lack of a significant difference in late cardiac toxicity”, but caution that “it is questionable whether even a 4000-patient trial has the statistical power to detect a difference in these important, but relatively rare, major cardiac events.”
“In addition, we know that cardiac toxicity can continue to manifest decades after radiotherapy”, they say.
Philip Poortmans and team write that “it seems reasonable to advise regional nodal irradiation to patients bearing the highest risk factors for regional lymph node involvement” while also considering patient age and comorbidity so as to “keep the assumed benefits in balance with possible side-effects”.
They conclude: “In the meantime, we are eagerly expecting the final analysis from the Early Breast Cancer Trialists’ Collaborative Group meta-analysis and updates from the other trials.
“As for our study, follow-up is continuing for up to 20 years with an expected last and final analysis in 2023.”
Poortmans PM, Weltens C, Fortpied C, et al. Internal mammary and medial supraclavicular lymph node chain irradiation in stage I–III breast cancer (EORTC 22922/10925): 15-year results of a randomised, phase 3 trial. Lancet Oncol; Advance online publication 2 November 2020. Doi: 10.1016/S1470-2045(20)30472-1.
Coles CE, Haviland JS, Kirby AM. Internal mammary node irradiation in breast cancer: does benefit outweigh risk? Lancet Oncol; Advance online publication 2 November 2020. Doi: 10.1016/S1470-2045(20)30551-9