In the JournalsPerspective

Nodal irradiation fails to improve OS following breast-conserving surgery

The addition of nodal irradiation to whole-breast irradiation did not improve OS but reduced recurrence rates among women with node-positive or high-risk node-negative early-stage breast cancer, according to study results.

A majority of women with early-stage breast cancer undergo breast-conserving surgery followed by whole-breast irradiation. Women with node-positive breast cancer who undergo mastectomy commonly also receive regional nodal irradiation — composed of radiotherapy to the chest wall and regional lymph nodes — to reduce locoregional and distant recurrence and improve OS, according to study background.

Timothy J. Whelan, BM, BCH, MSc, professor of oncology and head of radiation oncology at McMaster University, and colleagues sought to determine whether the addition of nodal irradiation to whole-breast irradiation would have the same effect in women undergoing breast-conserving surgery as it does it women undergoing mastectomy.

The researchers randomly assigned 1,832 women with node-positive or high-grade node-negative early-stage breast cancer undergoing breast-conserving surgery and adjuvant systemic therapy between 2000 and 2007 to whole-breast irradiation with or without regional nodal irradiation (n = 916 for each group).

OS served as the primary endpoint. DFS, isolated locoregional DFS and distant DFS served as secondary endpoints.

The median follow-up was 9.5 years.

The researchers observed no significant between-group difference in OS at the 10-year follow up (82.8% vs. 81.8%; HR = 0.91; 95% CI, 0.72-1.13). In a prespecified subgroup analysis, patients with ER-negative disease in the total irradiation arm exhibited higher OS rates (81.3% vs. 73.9%; HR = 0.69; 95% CI, 0.47-1).

However, women in the nodal irradiation arm experienced significantly improved DFS rates (82% vs. 77%; HR = 0.76; 95% CI, 0.61-0.94). Patients undergoing nodal irradiation also exhibited higher rates of isolated DFS (95.2% vs. 92.2%; P = .009) and distant DFS (86.3% vs. 82.4%; P = .03).

Patients undergoing nodal irradiation experienced higher rates of grade 2 or worse acute pneumonitis (1.2% vs. 0.2%; P = 0.1) and lymphedema (8.4% vs. 4.5%; P = .001).

“Our findings indicate the importance of basing treatment decisions on a careful discussion of the potential benefits and risks with each patient,” Whelan and colleagues concluded.

Harold J. Burstein, MD, PhD

Harold J. Burstein

Scientific and medical advancements could hold the key to identifying which patients may benefit from nodal irradiation, Harold J. Burstein, MD, PhD, senior physician at Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School, and Monica Morrow, MD, chief of breast service at Memorial Sloan Kettering Cancer Center, wrote in an accompanying editorial.

Monica Morrow, MD

Monica Morrow

“Our recommendations with respect to radiotherapy have historically been based solely on disease burden without substantial consideration of the effect of systemic therapy and tumor subtype on local recurrence,” Burstein and Morrow wrote. “A growing number of studies suggest that genomic profiling could be a more reliable predictor of local recurrence than tumor stage or other traditional clinical factors and hence holds the promise for more refined approaches to regional radiotherapy.” – by Cameron Kelsall

Disclosure: Please see the full study for a list of all researchers’ relevant financial disclosures.

The addition of nodal irradiation to whole-breast irradiation did not improve OS but reduced recurrence rates among women with node-positive or high-risk node-negative early-stage breast cancer, according to study results.

A majority of women with early-stage breast cancer undergo breast-conserving surgery followed by whole-breast irradiation. Women with node-positive breast cancer who undergo mastectomy commonly also receive regional nodal irradiation — composed of radiotherapy to the chest wall and regional lymph nodes — to reduce locoregional and distant recurrence and improve OS, according to study background.

Timothy J. Whelan, BM, BCH, MSc, professor of oncology and head of radiation oncology at McMaster University, and colleagues sought to determine whether the addition of nodal irradiation to whole-breast irradiation would have the same effect in women undergoing breast-conserving surgery as it does it women undergoing mastectomy.

The researchers randomly assigned 1,832 women with node-positive or high-grade node-negative early-stage breast cancer undergoing breast-conserving surgery and adjuvant systemic therapy between 2000 and 2007 to whole-breast irradiation with or without regional nodal irradiation (n = 916 for each group).

OS served as the primary endpoint. DFS, isolated locoregional DFS and distant DFS served as secondary endpoints.

The median follow-up was 9.5 years.

The researchers observed no significant between-group difference in OS at the 10-year follow up (82.8% vs. 81.8%; HR = 0.91; 95% CI, 0.72-1.13). In a prespecified subgroup analysis, patients with ER-negative disease in the total irradiation arm exhibited higher OS rates (81.3% vs. 73.9%; HR = 0.69; 95% CI, 0.47-1).

However, women in the nodal irradiation arm experienced significantly improved DFS rates (82% vs. 77%; HR = 0.76; 95% CI, 0.61-0.94). Patients undergoing nodal irradiation also exhibited higher rates of isolated DFS (95.2% vs. 92.2%; P = .009) and distant DFS (86.3% vs. 82.4%; P = .03).

Patients undergoing nodal irradiation experienced higher rates of grade 2 or worse acute pneumonitis (1.2% vs. 0.2%; P = 0.1) and lymphedema (8.4% vs. 4.5%; P = .001).

“Our findings indicate the importance of basing treatment decisions on a careful discussion of the potential benefits and risks with each patient,” Whelan and colleagues concluded.

Harold J. Burstein, MD, PhD

Harold J. Burstein

Scientific and medical advancements could hold the key to identifying which patients may benefit from nodal irradiation, Harold J. Burstein, MD, PhD, senior physician at Dana-Farber Cancer Institute and associate professor of medicine at Harvard Medical School, and Monica Morrow, MD, chief of breast service at Memorial Sloan Kettering Cancer Center, wrote in an accompanying editorial.

Monica Morrow, MD

Monica Morrow

“Our recommendations with respect to radiotherapy have historically been based solely on disease burden without substantial consideration of the effect of systemic therapy and tumor subtype on local recurrence,” Burstein and Morrow wrote. “A growing number of studies suggest that genomic profiling could be a more reliable predictor of local recurrence than tumor stage or other traditional clinical factors and hence holds the promise for more refined approaches to regional radiotherapy.” – by Cameron Kelsall

Disclosure: Please see the full study for a list of all researchers’ relevant financial disclosures.

    Perspective
    Shelly Bowers Hayes

    Shelly Bowers Hayes

    This study by Whelan and colleagues reports the results of the Canadian MA.20 randomized trial of 1,832 women with node-positive or high-risk node-negative disease who underwent breast-conserving surgery. Researchers defined "high risk" as a primary tumor size of at least 5 cm, or 2 cm with fewer than 10 axillary nodes removed and at least one of the following: grade 3 histology, ER-negative disease or lymphovascular invasion. Researchers randomly assigned patients after lumpectomy to whole-breast radiation alone or whole-breast radiation plus regional nodal irradiation (axilla, supraclavicular and internal mammary nodes). All patients received systemic therapy consisting of chemotherapy, hormone therapy or both. 

    This study shows that radiating the regional lymph nodes in addition to the breast in patients with node-positive or high-risk node-negative breast cancer after lumpectomy improves DFS at 10 years. The risks for cardiac and pulmonary complications were slightly higher in the nodal irradiation group, but these risks were very low overall and deaths from cardiovascular causes were identical in both groups.

    This is a much anticipated paper, as this study was presented in abstract form several years ago and the breast oncology community has been eagerly anticipating the full manuscript. The treatment of the regional lymph nodes in breast cancer, both surgically and with radiation, is rapidly evolving and this paper adds to this evolution. Radiation to the regional lymph nodes is known to minimize the risk for recurrence in the nodes, but the survival benefit of comprehensive regional nodal irradiation in the breast conservation setting is not well defined. I believe that this paper is thought-provoking and likely there will be additional randomized trials, perhaps in the U.S., attempting to corroborate these findings. This study suggests that physicians should strongly consider comprehensive regional nodal irradiation in patients who fit the criteria of this study.

    • Shelly Bowers Hayes, MD
    • Fox Chase Cancer Center

    Disclosures: Hayes reports no relevant financial disclosures.