CHICAGO (EGMN) - Adding regional nodal irradiation to whole-breast irradiation significantly improved disease-free survival, but not overall survival in a randomized multi-center phase III trial of women with node-positive or high-risk node-negative disease treated with breast-conserving surgery and adjuvant therapy.
An interim analysis of 1,832 women with breast cancer found that after a median follow-up of 62 months, whole breast irradiation (WBI) plus regional nodal irradiation (RNI) significantly reduced the risk of locoregional recurrence from 5.5% to 3.2% (P = .02; hazard ratio 0.8) and distant recurrence from 13% to 7.6% (P = .002; HR 0.64), lead investigator Dr. Timothy Whelan reported at the annual meeting of the American Society of Clinical Oncology.
Overall survival in the intergroup trial was 9.3% with WBI vs. 7.7% with the combined radiation regimen, but the difference did not reach statistical significance (P = .07; HR 0.76).
In view of the positive findings, the data safety monitoring committee recommended that the results be released, Dr. Whelan told reporters at a press briefing during the meeting.
He suggested that the findings could expand the pool of women offered RNI. Currently, ASCO and the American Society for Therapeutic Radiology and Oncology (ASTRO) guidelines recommend locoregional radiation following mastectomy for tumors greater than 5 cm or with more than three positive axillary nodes.
Of the 1,832 women enrolled in the National Cancer Institute of Canada Clinical Trials Group MA.20 trial, 85% had one to three positive lymph nodes, and 10% had high-risk, node-negative breast cancer. All women were treated with breast-conserving surgery plus adjuvant chemotherapy or endocrine therapy.
"Results from MA.20 suggest that all women with node-positive disease be offered regional node irradiation provided they are made aware of the associated toxicities," said Dr. Whelan, head of radiation oncology at McMaster University and the Juravinski Cancer Centre, Hamilton, Ont.
The addition of RNI to WBI significantly increased the rates of grade 2 or higher dermatitis from 40% to 50% (P less than .001), pneumonitis from 0.2% to 1.3% (P = .01), and lymphedema from 4% to 7% (P = .004). The lymphedema was primarily grade 2, Dr. Whelen pointed out.
Reporters questioned why an earlier unpublished French study did not find a benefit with RNI, while MA.20 did. Dr. Whelan responded that regional radiation in the earlier study was limited to the internal mammary lymph nodes alone, whereas MA.20 expanded the upper radiation field to include the upper internal mammary nodes, supraclavicular nodes, and high axillary nodes. He could not explain why overall survival was not improved.
Radiation dosages for WBI were 50 Gy in 25 fractions plus a boost at the discretion of the cancer center of 10 Gy in 5 fractions. The RNI dosage was 45 Gy in 25 fractions.
WBI and RNI were delivered concurrently, so the added therapy would not require additional office visits for women, and would modestly lengthen the therapy.
The researchers will continue to monitor the patients and evaluate new techniques to reduce potential side effects, he said in an interview.
MA.20 was sponsored by the Canadian Cancer Society Research Institute, National Cancer Institute/Cancer Therapy Evaluation Program, and Canadian Breast Cancer Research Alliance. Dr. Whelan and his coauthors disclosed no conflicts of interest.