Quality of Postmastectomy Radiation Therapy Affects SurvivalKey Words
Breast cancer, mastectomy, radiation therapy. (Definitions of many terms related to cancer can be found in the Cancer.gov Dictionary.)
Summary
Radiation therapy after mastectomy for breast cancer increases both five-year and 10-year survival for women at high risk of recurrence, as long as such treatment is of appropriate quality. Radiation therapy using too little or too much radiation, or failing to treat all areas at risk of recurrence, does not increase survival. The finding comes from an analysis combining the results of 36 randomized breast cancer clinical trials.
Source
Journal of the National Cancer Institute, Jan. 4, 2006 (see the journal abstract).
(J Natl Cancer Inst. 2006 Jan 4;98(1):26-38)
Background
The benefits and risks of radiation therapy for breast cancer following full mastectomy have been examined extensively. Although radiation therapy reduces the risk of local recurrence (in the area close to the original tumor), most previous studies have not shown a corresponding increase in survival in these patients. In fact, some studies have suggested that the late health effects of radiation may offset any gains in survival.
However, these previous studies have not taken into account the quality of the radiation therapy given - that is, whether or not doctors used the dosage and targets currently accepted as appropriate. If only the presence or absence of radiation therapy is considered, the benefits may be underestimated.
The Study
When researchers combine data from multiple studies, it’s called a meta-analysis. Here, the authors looked at any randomized controlled trial that had been included in earlier meta-analyses and systematic reviews of radiation therapy.
The only ones they kept in their own meta-analysis were those in which the patients had operable breast cancer that was initially treated with mastectomy and whose study design compared postmastectomy radiation with no radiation. None of the trials could have confounding factors, such as one group getting chemotherapy when its comparison group did not.
Thirty-six trials made the cut, which included data on more than 13,000 women. Each trial was grouped into one of three categories:
- optimal radiation therapy, defined as following modern dose and target guidelines
- inadequate or excessive radiation therapy
- incomplete tissue coverage
Because of the way they were designed, the 36 trials allowed for 38 unconfounded radiotherapy vs. no radiotherapy comparisons. Twenty-five comparisons involved optimal radiation therapy, seven used inadequate or excessive radiation therapy, and six had incomplete tissue coverage.
Twenty-six had five-year survival data and 19 had 10-year survival data, which the investigators analyzed to see whether the quality of radiation therapy given after mastectomy affected survival.
Val Gebski, M.Stat., of the National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Australia, was the lead author of the report.
Results
The authors’ meta-analysis showed a statistically significant 2.9 percent absolute increase in five-year survival for patients receiving optimal radiation therapy. This increase in survival rose to 6.4 percent at 10 years after treatment.
In contrast, no significant increase in survival was found in patients receiving inadequate or excessive radiation therapy or incomplete tissue coverage.
Among high risk women alone (those whose cancer had spread to the lymph nodes), there was a 5.2 percent increase in 10-year survival after optimal radiation therapy.
In a second analysis of all patients that excluded three trials with inappropriate randomization schemes, the increases in survival after optimal radiation therapy were even higher: 3.4 percent at five years after therapy and 7.1 percent at 10 years after therapy.
An increase in nonbreast cancer death was noticed in the groups receiving any category of radiation therapy, but for optimal therapy this was overshadowed by the survival benefit. The investigators applied their findings to hypothetical patients with different risks of recurrence and death. They determined that a low-risk patient receiving optimal radiation therapy has a 2.6 percent absolute reduction in the risk of death from any cause, while a high-risk patient has an 11 percent absolute reduction.
Limitations
Five-year and 10-year survival data were missing for several of the trials, which, as the authors state, “may have led to a biased estimate in favor of postoperative radiation therapy.”
On the other hand, note Leonard Prosnitz, M.D., and Lawrence Marks, M.D., in an accompanying editorial, the inclusion of studies that did not include chemotherapy or hormonal therapy (which improve survival) and the inclusion of patients at low risk of recurrence might have caused an underestimation of the survival benefits of radiation therapy.
The authors also note that their survival analyses stop after 10 years of follow up. Because some late cardiac effects of radiation therapy can occur more than 10 years after treatment, this could cause underestimation of radiation-related mortality. However, modern treatment planning and equipment can now greatly reduce the dose to the heart during treatment compared to the doses given at the time the trials were conducted.
Comments
Despite the limitations of the study, “the authors make a valuable contribution by addressing the quality issue and convincingly demonstrate a statistically significant increase in survival as well as local-regional control in patients treated with optimal postmastectomy radiation therapy, compared with those receiving inappropriate or no postmastectomy radiation therapy” say Prosnitz and Marks.
“This analysis shows that, though no one paper shows a significant advantage for high-risk patients, when you look at the literature as a whole, there is a benefit,” says Anurag Singh, M.D., a radiation oncologist with the National Cancer Institute’s Center for Cancer Research. “Postmastectomy radiation therapy done properly benefits patients at risk for recurrence.”
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