KEY POINTS
- This mid-trial analysis of the ongoing KROG 19-09 prospective cohort included 366 patients from eight institutions, all initially cT1-3N1, rendered ypN0 after neoadjuvant chemotherapy, breast-conserving surgery and sentinel-node biopsy. 176 were assigned to whole-breast plus regional nodal irradiation and 190 to whole-breast irradiation alone.
- Treatment was heterogeneous even before examining individual nodal doses: 39.9% received 3D conformal RT and 60.1% IMRT. Half of the cohort (50.3%) achieved a complete pathological response after neoadjuvant treatment.
- In patients assigned to regional nodal irradiation, 14% were dosimetric outliers for axillary level II D95% and 17% for level III. Unexpected dose variation was also present in the whole-breast-only group, where 9% and 8% were outliers for levels II and III, respectively.
- The variation was strongly physician-dependent. For one physician, 7 of 12 patients (58%) receiving regional nodal irradiation were outliers for axillary level III. For another, 21 of 49 patients (43%) were outliers for both levels II and III.
- The problem was not limited to small numerical deviations. Some plans categorized as regional nodal irradiation used high tangents covering mainly axillary level I and part of level II, without level III or supraclavicular coverage. Across the nodal-RT cohort, supraclavicular D95% ranged from 0% to 106% of the prescription, illustrating how differently the same treatment label could be implemented.
- Breast-target deviations were also substantial: 34 patients (19%) in the nodal-RT group and 40 (21%) in the whole-breast-only group were breast CTV outliers. Figure 3 showed that several of these plans effectively used partial-breast approaches; 36 previously treated patients had received partial-breast irradiation despite this being considered incompatible with the study population.
- Organ-at-risk variation showed another physician-level signal. Eight left-sided patients received mean heart doses of 10–19 Gy and seven right-sided patients 5–9 Gy; 14 of these 15 cases were treated by one physician. The investigators subsequently modified trial procedures and plan to relate actual regional nodal dose, rather than group allocation alone, to eventual clinical outcomes.
CLINICAL TAKEAWAY
KROG 19-09 exposes an important problem in radiation trials: “regional nodal irradiation” on a case-report form does not guarantee that the same nodal volumes were actually treated. The final clinical analysis will therefore need delivered-dose information to avoid attributing outcomes to treatment groups that were dosimetrically much less distinct than intended.