November 11, 2011 — Not all women with node-positive breast cancer need axillary lymph node dissection (ALND). This revelation came from the American College of Surgeons Oncology Group (ASCOG) Z0011 trial, which was published in February to great fanfare (JAMA. 2011;305:569-575), and represents a change in a surgical standard of care.
Now, a group of radiation oncologists have written an essay on the implications of the Z0011 findings for their field.
The essay, published online October 31 in the Journal of Clinical Oncology, includes a table with suggested approaches to radiation field design in patients who are node-positive but who will not undergo ALND.
The Z0011 trial demonstrated equivalent 8-year survival in patients with breast cancer and 1 or 2 positive sentinel lymph nodes (SLNs) who were randomly assigned to SLN biopsy alone or SLN biopsy followed by ALND. The finding was considered a victory for the patients who will be able to avoid ALND and its morbidity risks.
All of the Z0011 patients had breast-conserving surgery and nearly all had some form of systemic therapy. They also had whole-breast irradiation with tangential fields, write the essayists, led by Bruce Haffty, MD, from the Robert Wood Johnson Medical School and Cancer Institute of New Jersey in New Brunswick. Regional nodal irradiation was not allowed in Z0011, they add.
The essayists believe that tangential field radiation played a part in the Z0011 results. They suspect that, in addition to systemic therapy helping to kill off nodal disease, "the tangential field radiation that was used to treat the breast coincidently delivered radiation treatment to the lower axilla and eradicated the disease."
Dr. Haffty and his coauthors are not alone in this suspicion.
When the Z0011 results were published earlier this year, 2 breast cancer experts wrote an accompanying editorial and addressed the issue of residual disease (JAMA. 2011;305:606-607). "Adjuvant radiation and systemic therapy likely treated the low-volume nodal metastasis in this study," wrote Grant Walter Carlson, MD, and William Wood, MD, from the Winship Cancer Institute of Emory University in Atlanta, Georgia.
Because of the role that whole-breast radiation with tangential fields played in the outcome of Z0011, Dr. Haffty and his coauthors believe 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 might not be included in the radiation fields.
Nomograms Can Help With the Uncertainty
The standard of care for patients with positive SLNs has traditionally been a completion ALND. This is important to radiation oncologists because they have "historically relied on ALND findings in the design of the radiation treatment fields," explain the essayists.
Z0011 throws a wrench into that. Now, they point out, "many patients with positive SLNs will forego ALND."
Radiation oncologists are currently without clear guidance on this matter. "There are no prospective data with respect to optimal radiation approaches for patients with positive SLNs who do not undergo ALND," they explain.
"The optimal design of radiation fields for patients with positive SLNs who do not undergo ALND is uncertain," they declare.
What to do? In search of answers, the essayists took a closer look at the Z0011 study.
Data from the ALND patients in the trial revealed that the risk for additional axillary disease was "relatively low" (27%). In contrast, a meta-analysis reported a 53% incidence of additional disease on ALND after a positive SLN biopsy (Cancer. 2006;106:4-16).
In other words, Z0011 "was enriched" with patients with a low burden of axillary disease, "which may also have contributed to the high regional control rate" in the trial, the essayists say. So the trial has to be taken with a grain of salt and treatment planning needs to be informed by that, the essayists explain.
Without ALND-related information, the radiation oncologist can assess the probability of residual disease burden with nomograms, they note.
"There are validated nomograms that estimate additional nodal involvement on the basis of tumor size, grade, histology, receptor status, lymphovascular invasion, number of positive SLNs, and other factors. In combination with clinical judgment, these data can be helpful in estimating the risk of additional positive nodes and guiding radiation field design," they write.
These nomograms were developed at the Memorial Sloan-Kettering Cancer Center in New York City and the University of Texas M.D. Anderson Cancer Center in Houston. The essayists used the nomograms to develop a table that describes a set of clinical scenarios, including the number of positive sentinel nodes, provides estimates of the probability of additional nodes being involved, and finally, recommends a field design.
Regional Irradiation: Individualize Treatment
It has been repeatedly shown that radiation is successful in controlling microscopic disease in the lymph nodes, and has improved disease-free and overall survival in node-positive breast cancer, the authors point out.
The value of regional nodal irradiation, say the essayists, has been recently confirmed in the National Cancer Institute of Canada (NCIC) Clinical Trials Group MA.20 trial.
In that trial, patients with high-risk node-negative and node-positive breast cancer were randomized to whole-breast irradiation with or without regional nodal irradiation.
The study, composed predominantly of patients with 1 to 3 positive nodes, demonstrated a significant improvement in disease-free survival, locoregional control, distant metastasis, and a trend toward improved survival in the regional nodal irradiation group.
When the results of MA.20 were first presented, at the 2011 American Society of Clinical Oncology meeting, the lead investigator told Medscape Medical News that they were "practice changing."
Some clinicians reported having already adopted regional nodal irradiation as part of their standard of care for all node-positive women, including those with 1 to 3 positive nodes.
"As an institutional policy, we have routinely done regional nodal irradiation in these patients for some years," said David E. Wazer, MD, from Rhode Island Hospital and Brown University in Providence.
Dr. Wazer said that all node-positive women should receive regional nodal irradiation, and that the study should be practice changing.
Another radiation oncologist called the study "intriguing," but suggested that clinicians make decisions about regional nodal irradiation in patients with 1 to 3 positive nodes on a case-by-case basis.
"This has been an area of controversy, with data to both support and not support the addition of regional nodal radiation in this subset of patients," said Sandy Anderson, MD, from Fox Chase Cancer Center in Philadelphia, Pennsylvania.
The authors have disclosed no relevant financial relationships.
J Clin Oncol. Published online October 31, 2011. Abstract
Now, a group of radiation oncologists have written an essay on the implications of the Z0011 findings for their field.
The essay, published online October 31 in the Journal of Clinical Oncology, includes a table with suggested approaches to radiation field design in patients who are node-positive but who will not undergo ALND.
The Z0011 trial demonstrated equivalent 8-year survival in patients with breast cancer and 1 or 2 positive sentinel lymph nodes (SLNs) who were randomly assigned to SLN biopsy alone or SLN biopsy followed by ALND. The finding was considered a victory for the patients who will be able to avoid ALND and its morbidity risks.
All of the Z0011 patients had breast-conserving surgery and nearly all had some form of systemic therapy. They also had whole-breast irradiation with tangential fields, write the essayists, led by Bruce Haffty, MD, from the Robert Wood Johnson Medical School and Cancer Institute of New Jersey in New Brunswick. Regional nodal irradiation was not allowed in Z0011, they add.
The essayists believe that tangential field radiation played a part in the Z0011 results. They suspect that, in addition to systemic therapy helping to kill off nodal disease, "the tangential field radiation that was used to treat the breast coincidently delivered radiation treatment to the lower axilla and eradicated the disease."
Dr. Haffty and his coauthors are not alone in this suspicion.
When the Z0011 results were published earlier this year, 2 breast cancer experts wrote an accompanying editorial and addressed the issue of residual disease (JAMA. 2011;305:606-607). "Adjuvant radiation and systemic therapy likely treated the low-volume nodal metastasis in this study," wrote Grant Walter Carlson, MD, and William Wood, MD, from the Winship Cancer Institute of Emory University in Atlanta, Georgia.
Because of the role that whole-breast radiation with tangential fields played in the outcome of Z0011, Dr. Haffty and his coauthors believe 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 might not be included in the radiation fields.
Nomograms Can Help With the Uncertainty
The standard of care for patients with positive SLNs has traditionally been a completion ALND. This is important to radiation oncologists because they have "historically relied on ALND findings in the design of the radiation treatment fields," explain the essayists.
Z0011 throws a wrench into that. Now, they point out, "many patients with positive SLNs will forego ALND."
Radiation oncologists are currently without clear guidance on this matter. "There are no prospective data with respect to optimal radiation approaches for patients with positive SLNs who do not undergo ALND," they explain.
"The optimal design of radiation fields for patients with positive SLNs who do not undergo ALND is uncertain," they declare.
What to do? In search of answers, the essayists took a closer look at the Z0011 study.
Data from the ALND patients in the trial revealed that the risk for additional axillary disease was "relatively low" (27%). In contrast, a meta-analysis reported a 53% incidence of additional disease on ALND after a positive SLN biopsy (Cancer. 2006;106:4-16).
In other words, Z0011 "was enriched" with patients with a low burden of axillary disease, "which may also have contributed to the high regional control rate" in the trial, the essayists say. So the trial has to be taken with a grain of salt and treatment planning needs to be informed by that, the essayists explain.
Without ALND-related information, the radiation oncologist can assess the probability of residual disease burden with nomograms, they note.
"There are validated nomograms that estimate additional nodal involvement on the basis of tumor size, grade, histology, receptor status, lymphovascular invasion, number of positive SLNs, and other factors. In combination with clinical judgment, these data can be helpful in estimating the risk of additional positive nodes and guiding radiation field design," they write.
These nomograms were developed at the Memorial Sloan-Kettering Cancer Center in New York City and the University of Texas M.D. Anderson Cancer Center in Houston. The essayists used the nomograms to develop a table that describes a set of clinical scenarios, including the number of positive sentinel nodes, provides estimates of the probability of additional nodes being involved, and finally, recommends a field design.
Regional Irradiation: Individualize Treatment
It has been repeatedly shown that radiation is successful in controlling microscopic disease in the lymph nodes, and has improved disease-free and overall survival in node-positive breast cancer, the authors point out.
The value of regional nodal irradiation, say the essayists, has been recently confirmed in the National Cancer Institute of Canada (NCIC) Clinical Trials Group MA.20 trial.
In that trial, patients with high-risk node-negative and node-positive breast cancer were randomized to whole-breast irradiation with or without regional nodal irradiation.
The study, composed predominantly of patients with 1 to 3 positive nodes, demonstrated a significant improvement in disease-free survival, locoregional control, distant metastasis, and a trend toward improved survival in the regional nodal irradiation group.
When the results of MA.20 were first presented, at the 2011 American Society of Clinical Oncology meeting, the lead investigator told Medscape Medical News that they were "practice changing."
Some clinicians reported having already adopted regional nodal irradiation as part of their standard of care for all node-positive women, including those with 1 to 3 positive nodes.
"As an institutional policy, we have routinely done regional nodal irradiation in these patients for some years," said David E. Wazer, MD, from Rhode Island Hospital and Brown University in Providence.
Dr. Wazer said that all node-positive women should receive regional nodal irradiation, and that the study should be practice changing.
Another radiation oncologist called the study "intriguing," but suggested that clinicians make decisions about regional nodal irradiation in patients with 1 to 3 positive nodes on a case-by-case basis.
"This has been an area of controversy, with data to both support and not support the addition of regional nodal radiation in this subset of patients," said Sandy Anderson, MD, from Fox Chase Cancer Center in Philadelphia, Pennsylvania.
The authors have disclosed no relevant financial relationships.
J Clin Oncol. Published online October 31, 2011. Abstract
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