RT After Mastectomy Reduces Recurrence Risk

HAMILTON, Ontario—A meta-analysis of published clinical trials, presented at the San Antonio Breast Cancer Symposium, supports the concept that locoregional radiation therapy after mastectomy in breast cancer patients treated with adjuvant systemic therapy reduces the risk of recurrence and improves overall survival.

Radiation therapy was associated with an odds ratio of 0.65 for recurrence, which proved highly significant (P = .00001), compared with patients who did not receive radiation therapy, and with an odds ratio of 0.80 for mortality, also highly significant (P = .0000).

“The results are consistent with previously published trials showing that locoregional radiation therapy after mastectomy reduces mortality in women treated with adjuvant systemic therapy,” said Timothy Whelan, MD, director of the Supportive Cancer Care Research Unit, Hamilton Regional Cancer Center.

The analysis focused on 18 published studies initiated between 1974 and 1982. The trials had to meet specific criteria: randomization, treatment by mastectomy and axillary node dissection for all patients, use of the same adjuvant systemic therapy in randomized treatment arms, and median follow-up of at least 5 years.

Two Large Danish Studies

The trials comprised a total of 6,367 patients. However, 13 of the trials had a modest size of less than 200 patients. By comparison, the two Danish studies involved 1,708 patients (N Engl J Med 337:949-955, 1997) and 1,375 patients (Radiother Oncol 48[suppl 1]:S78, 1998).

Median follow-up ranged between 7.5 and 14 years. Most of the trials included patients who had positive lymph nodes, and in the majority of trials, a modified radical mastectomy and Level I axillary dissection were employed. Adjuvant systemic therapies included CMF, anthracycline-based regimens, other chemotherapy combinations, chemo-endocrine therapies, and tamoxifen (Nolvadex).

In the majority of studies, patients had radiation therapy to the chest wall, supra-clavicular, axilla, and internal mammary nodal areas. The radiation dose ranged between 36.5 and 50 Gy, administered in 12 to 25 fractions. Radiation therapy preceded chemotherapy in five trials, was given between cycles in four, was concurrent in three, and followed chemotherapy in three. Timing of radiation therapy was unknown in three trials.

When the two large Danish studies were removed from statistical consideration, the result was an odds ratio of 0.89 for recurrence and mortality, which was not significant. Both studies employed total mastectomy plus Level 1 axillary node dissection, and the total radiation dose was 50 Gy, delivered in 25 fractions.

“We weren’t able to compare the specifics of the trials, so we can’t be sure what factors in the two Danish studies might have influenced the overall results,” Dr. Whelan said. “The Danish studies were unique in that the investigators in both trials used good radiation therapy technique. In particular, they avoided cardiac irradiation, and that might be why the studies were so positive. Clearly, irradiation that involves a lot of cardiac treatment can cause ischemic heart disease.”

He suggested that “physicians who are interested in incorporating locoregional radiation therapy into clinical practice should take note of the specifics of the Danish studies.”

Dr. Whelan also conducted an exploratory analysis of factors potentially associated with a positive treatment effect. The analysis was limited by low statistical power and the fact that indirect comparisons were used, but the timing of radiation therapy (less than 6 months before the start of chemotherapy vs longer) proved to be a significant positive factor.

Omission of internal mammary radiation and use of anthracycline chemotherapy emerged as potentially negative influences on the treatment effect.