Nomogram-Based Estimate of Axillary Nodal Involvement in ACOSOG Z0011 (Alliance): Validation and Association with Radiation Protocol Variations and Outcomes

Abstract

Nomograms may be more accurate than experts at predicting risk. Our aim is to use two validated nomograms for axillary node involvement in breast cancer to assess whether protocol variations occurred in higher risk patients in ACOSOG Z0011. We used the M.D. Anderson (MDA) and Memorial Sloan-Kettering (MSK) nomograms to calculate the estimated risk of additional positive axillary nodes using sentinel lymph node biopsy and primary tumor surgery information. In the control arm, we compared findings of axillary dissection (AD) to nomogram-predicted estimates for validation. Logistic regression was used to evaluate whether nomogram-estimated higher risk of nodal involvement was associated with high tangent (HT) or supraclavicular (SCV) radiation field use for patients with known radiation field design. We included radiation fields in multivariate Cox models to evaluate associations with ten-year local-regional failure (LRF), disease-free survival (DFS), and overall survival (OS). Of the 856 evaluable women enrolled, 552 (64.5%) had complete details for the MDA nomogram. Mean MDA risk estimate for patients in both treatment arms was 23.8%. For patients on the AD arm with positive nodes, the estimated risk was 25.9%. Estimated risk did not significantly differ between treatment arms (p-value 0.16). Higher risk estimate was associated with additional positive nodes in the AD arm (OR: 1.04, 95% CI:1.02-1.06, p<0.0001). 78/165 (47.3%) of evaluable patients in the pooled arms with known radiation fields received either HT(n=53) or SCV(n=25) radiation. We observed significant association with higher MDA nomogram estimated risk and SCV radiation (OR=1.07, 95%CI: 1.04-1.10,p<0.0001) but not HT (OR=0.99, 95%CI:0.96-1.02,p=0.52). On multivariable analysis, MDA nomogram estimate was associated with LRF (HR=1.05, 95%CI:1.02-1.08, p=0.003) but not DFS (HR-1.00, 95%CI:0.9901.02, p=0.54) or OS (HR=1.00, 95%CI:0.99-1.02, p=0.66). Receiving SCV radiation was associated with worse DFS (HR=1.83, 95%CI:0.77-4.36, p=0.045) and OS (HR=2.72, 95%CI:1.03-7.18, p=0.027) but not LRF (p=0.27) The MSK nomogram had similar associations for all endpoints. MDA and MSK nomogram risk estimates were associated with confirmed additional lymph node risk in ACOSOG Z011 in the AD arm and appeared balanced in both arms. Radiation oncologists’ use of SCV fields was associated with treating higher risk patients with a worse prognosis.