Unlike previous post-mastectomy RT trials which included regional nodal irradiation (BC, Danish, etc), SUPREMO primarily tested chest wall RT only. Let’s compare to 4 other studies which found that RNI for LN+ after ALND can reduce DM. 1/
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SUPREMO: mastectomy pts with T1-2N1 (after ALND) or high risk T2N0 were randomized to CW RT or not. But only 12% got regional nodal irradiation to supraclavicular (SCV) and 1.5% to internal mammary nodes (IMN). 2/
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It’s interesting how FEW pts on SUPREMO got RNI even though it was permitted. I suspect the lack of RNI (and a lower risk cohort: 25% were N0) explains why it was a negative trial. Great thread from @BLawenda details more: x.com/BLawenda/status/198718… 3/
When the New England Journal of Medicine published the SUPREMO trial this week, social media lit up with headlines like:
“Radiotherapy after mastectomy can be avoided, study finds”
It’s an appealing headline, but dangerously incomplete.
brianlawenda.substack.com/p/…
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NCIC MA.20: after lumpectomy & ALND, pts with LN+ or high risk T2N0 all got whole breast irradiation (WBI), & randomized to RNI or not. WBI is like CW-only PMRT – the low axillary LNs are only incidentally radiated. 4/
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So the intervention arm of SUPREMO (CW RT, almost 90% without RNI) was analogous to the standard arm of MA.20 (WBI without RNI). Unfortunately a missed opportunity to see the effect of PMRT to CW *with* RNI in this population. 5/
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Both SUPREMO & MA.20 were recent trials with modern chemo, in similarly stages of patients (N0 25% & 10%, N1 75% & 85%, resp). SUPREMO found no DFS or DM benefit to CW RT, with just a small reduction in LRR (1.4%). 6/
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MA.20 suggests that the impact of RNI is to sterilize microscopic nodal mets which act as nidus for DM, i.e. DM are not simply a downstream consequence of LRR. So in this modern population, LRR and DM events appear to be "decoupled" - contrary to older data. 8/
Nov 9, 2025 · 12:52 PM UTC
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Other data corroborate the role of RNI in breast cancer: EORTC 22922: better DFS and DM with RNI to SCV/IMNs. Korean KROG 08-06: medial tumors w/ LN+ had better DFS & DMFS with IMNI. Danish DBCG-IMN1 and IMN2: better OS, DM & BCM with IMNI. 9/
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The SUPREMO results should NOT spell the end of PMRT for pN1 breast cancer after ALND. PMRT (if used) should include comprehensive RNI - CW only RT likely insufficient. But exactly WHICH patients need PMRT remains unclear. 10/
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I particularly favor PMRT (CW + RNI) for pN1 (after ALND) with medial location or those not receiving optimal systemic therapy. The risk calculator by Sittenfeld et al can help estimate individual risk: riskcalc.org/BreastPMRT 11/
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Of course, as ALND is increasingly abandoned in favor of SLNB alone, the role of RNI becomes more important as >30% of SLN+ have additional ALN+ that would go untreated. x.com/RTendulkarMD/status/19… 12/
Patients on SUPREMO had median 14 lymph nodes removed, so PMRT adds little value for pT1-2N1 after ALND. If ALND not done for SLN+, PMRT still indicated since >30% have risk of additional LN+ per AMAROS & SENOMAC. ASCO guidelines summarize nicely: ascopubs.org/doi/10.1200/JCO…
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