HAMILTON, OntarioA 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 werent able to compare the specifics of the trials, so
we cant 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