Positive Sentinel Nodes Without Axillary Dissection: Implications for the Radiation Oncologist

The recent publication of the results of the American College of Surgeons Oncology Group trial Z0011 has generated substantial interest in the medical community and public press. This trial demonstrated equivalent survival in patients with breast cancer and one to two positive sentinel lymph nodes (SLNs) who were randomly assigned to SLN biopsy (SLNB) alone or SLNB followed by axillary lymph node dissection (ALND). Equally important, regional recurrence with SLNB alone was less than 1%, despite the fact that an estimated 27% of patients had additional metastases in the undissected axillary nodes. All patients underwent breast-conserving surgery (BCS), systemic therapy as appropriate, and whole-breast irradiation (WBRT) with tangential fields (TFs). Regional nodal irradiation (RNI) was not allowed in Z0011. The standard of care for patients with positive SLNs has traditionally been a completion ALND. This results in excellent regional control and provides information that can guide treatment decisions for the radiation and medical oncologists. Because systemic therapy decisions increasingly rely on tumor size, grade, receptor status, and a variety of molecular profiles, there has been less dependence on the number of positive nodes for systemic therapy decision making. The radiation oncologist, however, has historically relied on ALND findings in the design of the radiation treatment fields; the number of positive nodes provides information concerning the risk of involvement of the level III/supraclavicular (SCV) nodes. When this risk is clinically relevant, radiation oncologists commonly treat the level III/SCV region with an SCV field. Typically this is used for patients with four or more positive nodes and selected patients with one to three positive nodes. With computed tomography–based planning, this involves contouring level I through III nodes, which ensures adequate radiation to the target nodes that are at risk. Although the combination of ALND and axillary radiation increases the risk of lymphedema, minimal morbidity is associated with radiation to the undissected level III/SCV region or to the undissected axilla. With the recent publication of Z0011, the optimal design of radiation fields for patients with positive SLNs who do not undergo ALND is uncertain. This will be increasingly important given that many patients with positive SLNs will forego ALND. In weighing whether such patients should receive RNI, it is important to consider the reason for the less than 1% regional recurrence rate in Z0011, despite the fact that an estimated 27% of patients had additional undissected positive nodes. Systemic therapy, which the majority of patients in Z0011 received, may have played a significant role. Studies of patients with positive nodes have demonstrated that approximately 25% of patients who are treated with chemotherapy have complete eradication of nodal disease. The long-term use of hormonal therapy may also contribute. It is also possible that the low regional recurrence rate is a reflection of the extensive processing of SLNs and subsequent detection of a burden of disease so low that it is held in check by the host immune system, analogous to patients with bone marrow micrometastases who never develop clinically evident metastases. A final possibility, and one that we believe is highly relevant, is that TF radiation that was used to treat the breast coincidently delivered radiation treatment to the lower axilla and eradicated the disease. If a large component of the axilla were in the TF region, this is likely to have contributed significantly. We believe that this observation is important and consequently that the results of Z0011 should not be extrapolated to patients who are treated with mastectomy without radiation, partial breast irradiation, irradiation of the breast in the prone position, intraoperative irradiation, or other techniques in which the axilla may not be included in the radiation fields. It is estimated that, using standard TFs, more than 50% of level I and 20% to 30% of level II nodes receive 95% of the prescribed radiation dose; this is dependent on patient anatomy and where the radiation oncologist sets the upper TF border. Although the Z0011 protocol did not allow RNI, the degree to which the TFs covered level I and II nodes, and whether the radiation oncologist placed the superior border of the TFs to treat more of the level I and II nodes (high tangents), was not documented in the trial. (Currently the American College of Surgeons Oncology Group is working to extract this data.) Although the contribution of high TFs to regional control in Z0011 remains uncertain, and the data that support the use of high TFs are based primarily on retrospective dosimetric studies, the use of high TFs has been shown in several studies to include the majority of level I and II nodes. There are several important points to make regarding Z0011 when considering the risk of additional positive nodes. First, patients who participated in this trial had favorable disease characteristics: the median age was 55 years, 70% had T1 tumors, 82% had estrogen receptor–positive disease, 71% had only one positive SLN, and 44% JOURNAL OF CLINICAL ONCOLOGY COMMENTS AND CONTROVERSIES VOLUME 29 NUMBER 34 DECEMBER 1 2011