br The axilla represented the most common site of
The axilla represented the most common site of NR (102/243). Few were outside of RTOG (14/102) or ESTRO (5/102) guidelines. Among those not encompassed by RTOG, most (7/14) occurred in the level 1 region before the axillary vessels formally cross the lateral border of pec-toralis minor or within the interpectoral region (5/14),
Fig. 2. Nodal relapse-free survival (RFS) among high-risk patients who underwent regional nodal irradiation (RNI; red ) and low-risk patients who did not receive RNI (blue). Log rank (Mantel-Cox) analysis was performed to assess for significant nodal RFS differences between curves (medial SCV Z 0.10; lateral SCV Z 0.009).
588 DeSelm et al. International Journal of Radiation Oncology Biology Physics
P Factor OR value
Abbreviations: ER Z RVX-208 receptor; IMN Z internal mammary node; LN Z lymph node; LVI Z lymphovascular invasion; OR Z odds ratio; SCV Z supraclavicular.
medial to the axillary vessels. One recurrence under the latissimus dorsi muscle and one over the latissimus dorsi were not encompassed by either guideline.
Predictors of nodal recurrence
Multivariable analysis of the effect of ER status, age, LVI, total number of positive nodes, and grade on NR-free sur-vival in each region of NR was performed (Table 3). LVI was most strongly associated with IMN NR (P Z .001) and grade 3 was associated with both IMN and SCV NR
Recurrence and survival outcomes
To assess the time-dependent association of clinicopatho-logic features with specific regions of NRs, we performed Kaplan-Meier analysis of time to failure among those who experienced NR, broken down by cohorts that were most significant on MVA. Relative to ER-positive patients, ER patients recurred more quickly in the SCV, axillary, and IMN regions. The 5-year IMN RFS is 92% for ER positive versus 70% for ER negative, but the 12-year IMN RFS was 69% for both ER positive and ER negative. In contrast, patients with grade 3 versus grade 1 or 2 disease (n Z 94) had a statistically lower rate of RFS in the SCV, axillary, and IMN regions across all time points (Fig. 3).
Nodal Recurrence Free Survival
Months to Recur
Fig. 3. Time to nodal recurrence by region, grade, extracapsular extension (ECE), and estrogen receptor (ER) status.
Abbreviations: ECE Z extracapsular extension; ER Z estrogen receptor; NR Z nodal recurrence. *P < .05.
No lsolated Regional
lsolated regional Recurrence
Months From 2 Year Landmark
Number at risk:
Axilla SCV IMN
Survival by Site of Recurrence
Months From 2 Year Landmark
Fig. 4. Overall survival by recurrence site. (A) Two-year landmark analysis from time of surgery, showing inferior overall survival among patients with nodal recurrence (NR; n Z 158) versus all patients (N Z 13,062). (B) Overall survival is inferior among patients with internal mammary node (IMN) NR, compared to patients with axillary NR and supraclavicular (SCV) NR. (C) Patients with IMN NR present with higher rates of concurrent distant metastasis (DM) relative to axillary NR and SCV NR groups.
of the increased presence of concurrent distant metastasis (DM) in patients with IMN recurrence compared with either axillary (P Z .002) or SCV (P Z .02; Fig. 4C).