Nomograms can outperform experts in predicting additional axillary nodal metastases in clinical N0 breast cancer patients with a positive sentinel node biopsy. In ACOSOG Z0011, prior analysis showed radiation (RT) fields showed that half of all patients with confirmed RT fields used high tangents and 19% include regional nodal irradiation. We sought to evaluate two hypotheses in this secondary analysis: 1. Nomograms are valid in Z0011 and confirm similar distribution of nodal risk in two treatment arms; 2. Radiation fields including lymph nodes were not in the highest risk patients despite best clinical judgment. I presented this research October 24, 2018 at the American Society for Radiation Oncology (ASTRO) Annual Meeting in San Antonio, Texas.

1. Patient Characteristics by Radiation Treatment Received (MDACC nomogram cohort)
MDACC and MSKCC nomogram estimates of additional positive
axillary nodes by treatment arm and observed nodal involvement in the
axillary dissection arm
Distribution of LN risk estimate for MDACC and MSKCC nomograms
LN risk estimate by ALND versus SLNBx with MDACC nomogram• We used the nomograms from M.D. Anderson Cancer
Center (MDACC) and Memorial Sloan-Kettering Cancer
Center (MSKCC) available on their websites summer 2017
• We compared MDACC and MSKCC nomogram estimates in
both treatment arms
• We used logistic regression to evaluate associations
between nomogram estimates and radiation fields
• We included radiation field design in multivariable Cox-
models for associations of radiation fields with 10-year
local-regional failure (LRF), disease-free survival (DFS),
and overall survival (OS) estimates
BACKGROUND RESULTS
• MDACC and MSKCC nomogram estimates are associated with
additional axillary lymph node risk in ACOSOG Z0011
• Findings at axillary dissection were similar to the mean estimated risk
of additional metastases using both nomograms
• Risk estimates were evenly distributed between treatment arms
• Use of a supraclavicular field was associated with worse survival,
likely related to clinical use in patients with differences in clinical risk
not captured by nomogram score alone
AIMS
• To evaluate nomogram accuracy in the axillary lymph node
dissection (ALND) arm
• To assess distribution of lymph node risk in both arms
• To determine whether patients radiation fields with nodal
irradiation had higher nomogram-based risk estimates or
different 10-year clinical outcomes
METHODS
CONCLUSIONS
Nomograms can outperform experts in predicting additional
axillary nodal metastases in clinical N0 breast cancer patients
with a positive sentinel node biopsy.
In ACOSOG Z0011, prior analysis showed radiation (RT) fields
showed that half of all patients with confirmed RT fields used
high tangents and 19% include regional nodal irradiation. We
sought to evaluate two hypotheses in this secondary analysis:
1. Nomograms are valid in Z0011 and confirm similar
distribution of nodal risk in two treatment arms;
2. Radiation fields including lymph nodes were not in the
highest risk patients despite best clinical judgment.
• Nomogram-Based Estimate of Axillary Nodal Involvement in ACOSOG Z0011: Validation and Association with
Radiation Protocol Variations and Outcomes
• Matthew S. Katz,1 Linda McCall,2 Karla Ballman,3 Bruce G. Haffty,4 Reshma Jagsi,5 Armando E. Giuliano6
• 1Department of Radiation Medicine, Lowell General Hospital, Lowell, MA; 2 Alliance Statistics and Data Center, Duke University, Durham, NC; 3 Department of Biostatistics, Weill Medical College, New York, NY; 4 Department of Radiation Oncology,
• Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; 5 Department of Radiation Oncology, University of Michigan Medical Center, Ann Arbor, MI; 6 Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA
0
5
10
15
20
25
30
0-5 5-10 10-15 15-20 20-25 25-30 30-40 40-50 50-70 70-100
%ofpatients
Nomogram Risk of Additional Positive LN
MDACC MSKCC
0
5
10
15
20
25
30
0-5 5-10 10-15 15-20 20-25 25-30 30-40 40-50 50-70 70-100
%ofpatients
MDACC Nomogram Risk of Additional Positive LN
ALND No ALND
RESULTS
MDACC MSKCC
AD
(n=283)
SLND
(n=269)
p-value
AD
(n=251)
SLND
(n=249)
p-value
Estimated risk (%) 0.16 0.054
Mean (95% CI)
23.8%
(21.8-25.8)
21.9%
(20.1-23.7)
23.1%
(21.2 – 24.9)
20.7%
(19.1 – 22.4)
Median (range)
20.4%
(0.0 – 91.3)
19.0%
(0.3 – 78.9)
19.0%
(1.8– 88)
17.0%
(2.8 – 79.5)
Histologically confirmed
mean risk (%)
25.9% N/A 23.4% N/A
Radiation Treatment Received p-value
Confirmed
Breast / High
Tangents RT
(n=140)
Confirmed
Supraclavicular
(SCV) RT
(n=25)
Confirmed
No RT
(n=65)
Confirmed
RT NOS
(n=204)
Age (years) 0.061
Median (range) 53 (36 – 80) 54 (32 – 90) 52 (30 – 87) 58 (25 – 85)
Tumor size (cm) 0.084
Median (range) 1.7 (0.3 – 6.0) 2.2 (0.0 – 4.0) 1.8 (0.1- 7.5) 1.7 (0.1 – 17.0)
Histologic type 0.040
Ductal 110 (78.6%) 24 (96.0%) 54 (83.1%) 172 (84.3%)
Lobular 9 (6.4%) 0 5 (7.7%) 18 (8.8%)
Mixed 12 (8.6%) 0 6 (9.2%) 5 (2.4%)
Other 9 (6.4%) 1 (4.0%) 0 9 (6.4%)
Missing/Unknown 0 0 0 0
ER/PR Status 0.91
Negative 24 (17.1%) 5 (20.0%) 9 (13.8%) 34 (16.7%)
Positive 90 (64.3%) 14 (56.0%) 40 (61.5%) 124 (60.8%)
Missing/Unknown 26 6 16 46
Modified Bloom-Richardson
Score
0.11
1 29 (20.7%) 4 (16.0%) 9 (13.8%) 45 (22.1%)
2 63 (45.0%) 10 (40.0%) 34 (52.3%) 72 (35.3%)
3 24 (17.1%) 8 (32.0%) 16 (24.6%) 57 (27.9%)
Missing/Unknown 24 3 6 30
Lymphovascular invasion 0.041
No 90 (64.3%) 16 (64.0%) 29 (44.6%) 128 (62.8%)
Yes 50 (35.7%) 9 (36.0%) 36 (55.4%) 76 (37.2%)
Missing/Unknown 0 0 0 0
Number of SLN removed 0.20
0 1 (0.7%) 0 0 0
1 21 (15.0%) 7 (28.0%) 15 (23.1%) 50 (24.5%)
2 35 (25.0%) 5 (20.0%) 16 (24.6%) 64 (31.4%)
3 or more 83 (59.3%) 13 (52.0%) 34 (52.3%) 90 (44.1%)
Missing/Unknown 0 0 0 0
Number of positive SLN <0.0001
0 1 (0.7%) 1 (4.0%) 0 5 (2.5%)
1 105 (75.0%) 11 (44.0%) 43 (66.1%) 159 (77.9%)
2 29 (20.7%) 6 (24.0%) 17 (26.2%) 26 (12.7%)
3 or more 1 (0.7%) 6 (24.0%) 2 (3.1%) 7 (3.4%)
Missing/Unknown 4 1 3 7
Number of positive nodes on
ALND (ALND arm only) 0.001*
0 50 (35.7%) 6 (24.0%) 23 (35.3%) 76 (37.3%)
1 8 (5.7%) 1 (4.0%) 2 (3.1%) 11 (4.9%)
2 1 (0.7%) 3 (12.0%) 2 (3.1%) 8 (3.9%)
3 or more 0 5 (20.0%) 3 (4.6%) 9 (4.4%)
Missing/Unknown 81 10 35 100
Multivariable analysis: No radiation or supraclavicular radiation is
associated with worse 10-year clinical outcomes
MSKCC Nomogram Score MDACC Nomogram Score
HR (95% CI) p-value HR (95% CI) p-value
Overall Survival
Nomogram Score 1.01 (0.99 – 1.03) 0.27 1.00 (0.99 – 1.02) 0.66
Arm 1.12 (0.62 – 2.02) 0.71 1.06 (0.62 – 1.83) 0.82
RT Arm*
No RT 1.80 (0.84 – 3.86)
0.002
1.87 (0.88 – 3.96)
0.027Confirmed SCV RT 3.25 (1.19 – 8.88) 2.72 (1.03 – 7.18)
Confirmed Radiation NOS 0.63 (0.30 – 1.31) 0.85 (0.43 – 1.65)
Disease-free Survival
Nomogram Score 1.01 (0.99 – 1.03) 0.24 1.00 (0.99 – 1.02) 0.54
Arm 0.95 (0.57 – 1.59) 0.85 0.89 (0.56 – 1.40) 0.61
RT Arm*
No RT 1.70 (0.87 – 3.32)
0.002
1.54 (0.81 – 2.93)
0.045Confirmed SCV RT 2.58 (1.05 – 6.37) 1.83 (0.77 – 4.36)
Confirmed RT NOS 0.64 (0.34 – 1.19) 0.73 (0.42 – 1.27)
Local-Regional Recurrence
Nomogram Score 1.03 (0.99 – 1.06) 0.075 1.02 (0.99 – 1.04) 0.24
Arm 0.69 (0.25 – 1.92) 0.47 0.58 (0.23 – 1.48) 0.26
RT Arm*
No RT 6.47 (1.29 – 32.43)
0.065
3.37 (1.02 – 11.12)
0.12Confirmed SCV RT --
Confirmed RT NOS 1.97 (0.41 – 9.42) 1.06 (0.35 – 3.24)
MSKCC MDACC
HR (95% CI) p-value HR (95% CI) p-value
Overall Survival
Nomogram Score 1.02 (1.00 – 1.06) 0.089 1.01 (0.99 – 1.04) 0.31
RT Arm*
No RT 1.11 (0.37 – 3.33)
0.019
1.11 (0.35 – 3.54)
0.75Confirmed SCV RT 6.57 (1.40 – 30.82) 2.04 (0.42 – 9.82)
Confirmed Radiation NOS 0.50 (0.18 – 1.37) 0.86 (0.36 – 2.08)
Disease-free Survival
Nomogram Score 1.02 (0.99 – 1.04) 0.23 1.01 (0.99 – 1.03) 0.21
RT Arm*
No RT 0.82 (0.29 – 2.35)
0.074
0.77 (0.25 – 2.33)
0.90Confirmed SCV RT 4.41 (0.98 – 19.85) 1.35 (0.30 – 6.21)
Confirmed RT NOS 0.57 (0.24 – 1.35) 0.86 (0.41 – 1.80)
Local-Regional Recurrence
Nomogram Score 1.05 (1.00 – 1.10) 0.066 1.04 (1.00 – 1.08) 0.046
RT Arm*
No RT 1.02 (0.09 – 11.44)
0.99
1.07 (0.11 – 10.36)
0.99Confirmed SCV RT --- ---
Confirmed RT NOS 0.91 (0.15 – 5.65) 0.75 (0.15 – 3.87)
Multivariable analysis: Association of RT treatment type and nomogram risk estimate
10-year clinical outcomes for SLND alone patients
RESULTS
* Confirmed Breast/High Tangents = Reference
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Questions or comments: Email Matthew.Katz@lowellgeneral.org or
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