Specialized Radiation Offers No Survival Benefit in Early Breast Cancer

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Elsevier Global Medical News. 2009 Nov 11, P Wendling

CHICAGO (EGMN) - The application of radiation to the hard-to-treat internal mammary chain lymph nodes after mastectomy did not improve survival in a phase III randomized trial in 1,453 women.

No subgroups seemed to benefit from internal mammary chain radiation therapy (IMC-RT), said Dr. Pascale Romestaing, who led the study and presented its findings during a plenary session at the annual meeting of the American Society for Radiation Oncology.

Overall survival at 10 years was 62.6% in women who were treated with IMC-RT added to standard postmastectomy radiation, compared with 59.3% in women who had standard postmastectomy radiation alone. The difference was not statistically significant.

"Today, although this study has some limitations and 10-year follow-up may be too short for survival and cardiac toxicity, we would not recommend to systematically irradiate the internal mammary chain," said Dr. Romestaing, a radiation oncologist with the Centre de Radiothérapie Mermoz, in Lyon, France.

Although the trial was unable to show a 10% survival benefit, it is possible that a smaller but still clinically relevant benefit exists, said Dr. Jennifer Bellon, who was invited to discuss the results. "This is an important but not definitive study, which still leaves the question of internal mammary node radiation unanswered," she said.

The ability of the trial to show a substantial survival benefit with IMC-RT was unlikely because the risk of internal mammary node involvement was low in the cohort, and there was a competing risk of distant metastases, said Dr. Bellon of the Dana-Farber Cancer Institute in Boston. She also observed that a recent Early Breast Cancer Trialists' Collaborative Group meta-analysis involving 42,000 women with breast cancer in 78 randomized treatment trials did not show an overall survival benefit until 15 years. In that analysis, 24 of the 25 postmastectomy studies included the internal mammary nodes (Lancet 2005;366:2087-106).

Known disadvantages of internal mammary node radiation include pulmonary and cardiac toxicity. Cardiac toxicity is "particularly worrisome with anthracyclines and newer systemic agents, such as trastuzumab" and generally increases with time from treatment, Dr. Bellon said.

No excess of cardiac toxicity was observed in the current study, Dr. Romestaing said. After 5 years of follow-up, there were seven grade 3/4 cardiac events in the IMC-RT arm and five in the surgery-only arm (both 0.01%). Lung toxicity was reported in no cases vs. one case, respectively, and skin toxicity in eight cases vs. one case.

IMC-RT consisted of 45 Gy in 20 fractions in a combination of photons (12.5 Gy) and electrons (32.5 Gy). The target field included the first five intercostal spaces at a depth of 2-3.5 cm.

All patients (mean age, 56.5 years) had newly diagnosed stage I-II breast cancers, with about 75% having positive axillary lymph nodes and 25% having a primary tumor in an internal or central location in the breast area. In all, 86% received systemic therapy at the discretion of their physician.
Future studies may provide more insight into the value of IMC radiation. The European Organisation for Research and Treatment of Cancer and the National Cancer Institute of Canada have recently completed large randomized trials looking at internal mammary and supraclavicular radiation, with both awaiting data maturation, Dr. Bellon said.

Dr. Romestaing and Dr. Bellon reported no conflicts of interest.

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