Timothy J. Whelan, BM BCh
Radiation therapy directed to the regional lymph nodes of women with early-stage breast cancer reduced distant disease recurrence in a randomized phase III trial that suggests guidelines developed 15 years ago should be altered, according to research presented at the Annual Meeting of the American Society of Clinical Oncology (ASCO) on Saturday.
The study establishes the benefits of regional nodal irradiation (RNI) in women who have 1 to 3 positive nodes after being treated with breast-conserving surgery (BCS), said Timothy J. Whelan, BM BCh, lead study investigator and a professor of Oncology and the division head of Radiation Oncology at McMaster University and the Juravinski Cancer Centre, Hamilton, Ontario.
“Regional radiation can have an impact,” Whelan said in an interview. “Doctors would want to discuss that with their patients and just let them know about those benefits but unfortunately some side effects as well.”
In the study, 1832 patients were randomly assigned to receive whole-breast irradiation (WBI) or WBI plus RNI. In both groups, WBI was delivered to the chest wall and regional lymph nodes at 50 Gy 25 fractions along with a boost of 10 Gy and 5 fractions.
RNI was expanded to the upper fields, including the supraclavicular and the high axilla, at a dose of 45 Gy and 25 fractions. Whelan said the RNI and WBI were administered during the same doctor visit.
The study was conducted at 50 cancer centers in Canada, the United States, and Australia, and an interim analysis at a median follow-up of 62 months was carried out in March.
Distant recurrence and locoregional recurrence were 7.6% and 3.2%, respectively, for those in the WBI plus RNI group, as opposed to 13% and 5.5%, respectively in the WBI group.
Overall, there was an improvement in disease-free survival for the group that received both radiation therapies, from 84% of those who received WBI to nearly 90% for those in the WBI plus RNI group.
Whelan said the study failed to show a statistically significant improvement in overall survival—the primary endpoint—but the trend pointed in that direction with more results to be released as follow-up continues.
The addition of RNI was associated with an increase in adverse events. In the WBI plus RNI group, Grade 2 or greater pneumonitis was 1.3% and lymphedema was 7%, as opposed to 0.2% and 4%, respectively, in the WBI group.
The results have the potential to be practice changing because women with 1 to 3 positive nodes typically are not offered RNI, Whelan indicated.
The protocol for treating women with node-positive disease is to perform BCS plus axillary lymph node dissection and then WBI with adjuvant chemotherapy or hormonal therapy.
Patients with tumors >5 cm or >3 positive nodes are recommended for RNI under current guidelines that ASCO and the American Society for Radiation Oncology developed, Whelan noted. He said prior trials had left unsettled the question of whether women with fewer nodes should also receive RNI.
“This study’s quite unique in that the vast majority of patients had 1 to 3 positive nodes,” Whelan said in an interview. “They’re patients who are more likely to develop distant metastases.”
That finding was “particularly compelling” to briefing moderator Andrew Seidman, MD, who described himself as “a medical oncologist charged with preventing distant metastases.“ He is a physician at Memorial Sloan-Kettering Cancer Center in New York and professor of Medicine at Weill Medical College of Cornell University.
The National Cancer Institute of Canada Clinical Trials Group along with 5 other cooperative groups supported the study.
Whelan TJ, Olivotto I, Ackerman I, et al. NCIC-CTG MA.20: an intergroup trial of regional nodal irradiation in early breast cancer. J Clin Oncol. 2011. (suppl; abstract LBA1003).