Partially wide answers.

Headline: Can we omit internal mammary nodes when delivering regional nodal irradiation for breast cancer?

The Study: What causes as much heartburn as deciding whether or not to include the IMN’s? Generating a good treatment plan that covers the IMN’s while not giving excess dose to the heart or lungs. In fact, we recently learned from long-term followup of EORTC 22922/10925 that RNI with IMN coverage improves breast cancer mortality at the cost of increased pulmonary fibrosis and cardiac events. The Korean Radiation Oncology Group is here with the trial we’ve all been waiting for–kinda. KROG 08-06 was a phase 3 study performed in multiple centers in South Korea to determine if the addition of IMN coverage to regional nodal irradiation improved disease-free survival. It randomized 747 patients who underwent up-front surgery (no neoadjuvant chemo) for lymph node positive breast cancer. They had axillary dissection with 8+ nodes removed and either breast-conserving surgery or mastectomy. Most patients also received adjuvant chemotherapy. They were randomized to RNI (45-50.4 Gy) with or without IMN coverage (mostly with partially wide tangents) and a tumor bed boost as indicated. At 7 years, the difference in DFS (85.3% with v 81.9% without) was not statistically significant. This was a point of criticism, though, as the trial was designed to show a 10% absolute difference in DFS even though RNI altogether only improved DFS ~3% in the EORTC trial and ~5% in MA.20. Also, the ~2% difference in breast cancer mortality (8.4% with IMN, 10.8% without) wasn’t significantly different in KROG 08-06, yet the 12.5% v 14.4% difference was significant in the EORTC trial. Regional recurrences were relatively low (<3%) compared to distant recurrences (~12%). In subgroup analysis, the difference in DFS was mainly driven by patients with central and medial tumor location who saw a more substantial improvement from 81.6→ 91.8%. There were no major differences in toxicity despite a numerically higher rate of pneumonitis with IMN coverage (6.1% v 3.2%). So, the KROG trial doesn’t definitively clarify whether IMN coverage should be routinely included or omitted. More likely, it reinforces the practice of identifying risk factors (such as location) that predict a greater absolute benefit from IMN coverage. 

TBL: KROG 08-06 showed that the potential benefit of adding IMN coverage to RNI is likely small in magnitude when applied to a broad patient population with node positive breast cancer. Other risk factors (particularly central or medial tumor location) may help select patients with a greater absolute benefit. | Kim, ASTRO & JAMA Oncol 2021