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| Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials Early Breast Cancer Trialists' Collaborative Group* (Information about collaborators is given at the end of the paper) Correspondence to: EBCTCG Secretariat, Clinical Trial Service Unit (CTSU), Radcliffe Infirmary, Oxford OX2 6HE, Summary Background The long-term effects of radiotherapy on mortality from breast cancer and other causes remain uncertain. Methods A meta-analysis was done of 10-year and 20-year results from 40 unconfounded randomised trials of radiotherapy for early breast cancer. It involved central review of individual patients' data on recurrence and cause-specific mortality from 20000 women, half with "node-positive" disease. Radiotherapy fields generally included not only chest wall (or breast) but also axillary, supraclavicular, and internal mammary nodes. Findings A reduction of approximately two-thirds in local recurrence was seen in all trials, largely independent of the type of patient or type of radiotherapy (8·8% vs 27·2% local recurrence by year 10). Hence, to assess effects on breast cancer mortality of substantially better local control, results from all trials were combined. Breast cancer mortality was reduced (2p=0·0001) but other, particularly vascular, mortality was increased (2p=0·0003), and overall 20-year survival was 37·1% with radiotherapy versus 35·9% control (2p=0·06). There was little effect on early deaths, but logrank analyses of later deaths indicate that, on average after year 2, radiotherapy reduced annual mortality rates from breast cancer by 13·2% (SE 2·5) but increased those from other causes by 21·2% (SE 5·4). Nodal status, age, and decade of follow-up strongly affected the ratio of breast cancer mortality to other mortality, and hence affected the ratio of absolute benefit to absolute hazard from these proportional changes in mortality. Interpretation Radiotherapy regimens able to produce the two-thirds reduction in local recurrence seen in these trials, but without long-term hazard, would be expected to produce an absolute increase in 20-year survival of about 24% (except for women at particularly low risk of local recurrence). The average hazard seen in these trials would, however, reduce this 20-year survival benefit in young women and reverse it in older women. Lancet 2000; 355: 175770 Explanatory article below: "Risks of Radiation May Outweigh Benefits in Some Breast Cancer Patients " By Merritt McKinney WESTPORT, May 19 (Reuters Health) - A meta-analysis of randomized trials of radiotherapy in breast cancer patients shows that the treatment is associated with reduced local recurrence and breast cancer mortality, but also with increased mortality due to other causes. For older women as well as women of any age who have a low risk of recurrence, the risks of radiation may outweigh the benefits, researchers report in the May 20th issue of The Lancet. Dr. Rory Collins, of the Clinical Trial Service Unit at Radcliffe Infirmary, in Oxford, England, and other members of the Early Breast Cancer Trialists' Collaborative Group reviewed the 10-year and 20-year results of 40 unconfounded, randomized radiotherapy trials that included 19,582 women. All of the trials began before 1990. Overall, radiation prevented about two thirds of local recurrence, regardless of patient characteristics or radiation type, Dr. Collins told Reuters Health. According to Dr. Collins, radiation therapy appears to translate into "moderate improvement in avoidance of breast cancer deaths." He noted that the benefits of radiation tended to be greater in node-positive women. When the results of all studies were combined, women who received radiation did not have lower breast cancer mortality in the first 2 years, but after that, the annual breast cancer mortality was about 13% lower than that of women who did not undergo radiation, according to the report. Despite the reduced breast cancer mortality associated with radiotherapy, however, overall mortality was actually higher in radiation-treated women. Beginning 2 years after randomization, the annual non-breast cancer mortality rate was 21.2% higher in women treated with radiation. This increased mortality "appeared chiefly to involve an excess of vascular deaths, perhaps due to inadvertent irradiation of the coronary, carotid or other major arteries," the authors write. Overall, the 20-year survival rate was 37.1% in women treated with radiation and 35.9% in controls. Based on 20-year survival, "There's a modest benefit [of radiation] for younger women with node-positive disease under age 50," Dr. Collins said. "For women who are at low risk of local recurrence...any benefit is small, less than 1%." According to Dr. Collins, for older women with node-positive cancer, deciding whether the benefits of radiation outweigh the hazards is difficult. But in the report, the researchers state that if radiation techniques, including ones that reduce carotid and intrathoracic exposure "can be shown to yield most of the benefit while avoiding most of the hazard, 20-year survival could be moderately improved in a wider range of patients." In an accompanying editorial, Dr. John M. Kurtz, of University Hospital in Geneva, Switzerland, notes that the radiation techniques used today differ greatly from those in the studies included in the review. Despite the differences and the lower overall mortality associated with radiation in the review, Dr. Kurtz concludes that "the results of the overview should be considered good news for radiotherapy, since they firmly establish the reductions attainable in the risks of total recurrence...and breast cancer mortality." He notes that the risk of vascular morbidity can probably be reduced by refinements in radiation technique. However, Dr. Kurtz believes that the results of this meta-analysis "should not dissuade clinicians from continuing to favor conservation surgery and to provide patients with the advantages of breast irradiation with tangential photon beams, which have not been clearly implicated as a cause of vascular mortality." ------------------------------------------------------------- Lancet 2000;355:1739-1740,1757-1770. Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: an overview of the randomised trials Early Breast Cancer Trialists' Collaborative Group* *Information about collaborators is given at the end of the paper Correspondence to: EBCTCG Secretariat, Clinical Trial Service Unit (CTSU), Radcliffe Infirmary, Oxford OX2 6HE, UK (e-mail:bc.overview@ctsu.ox.ac.uk) Summary Background The long-term effects of radiotherapy on mortality from breast cancer and other causes remain uncertain. Methods A meta-analysis was done of 10-year and 20-year results from 40 unconfounded randomised trials of radiotherapy for early breast cancer. It involved central review of individual patients' data on recurrence and cause-specific mortality from 20000 women, half with "node-positive" disease. Radiotherapy fields generally included not only chest wall (or breast) but also axillary, supraclavicular, and internal mammary nodes. Findings A reduction of approximately two-thirds in local recurrence was seen in all trials, largely independent of the type of patient or type of radiotherapy (8·8% vs 27·2% local recurrence by year 10). Hence, to assess effects on breast cancer mortality of substantially better local control, results from all trials were combined. Breast cancer mortality was reduced (2p=0·0001) but other, particularly vascular, mortality was increased (2p=0·0003), and overall 20-year survival was 37·1% with radiotherapy versus 35·9% control (2p=0·06). There was little effect on early deaths, but logrank analyses of later deaths indicate that, on average after year 2, radiotherapy reduced annual mortality rates from breast cancer by 13·2% (SE 2·5) but increased those from other causes by 21·2% (SE 5·4). Nodal status, age, and decade of follow-up strongly affected the ratio of breast cancer mortality to other mortality, and hence affected the ratio of absolute benefit to absolute hazard from these proportional changes in mortality. Interpretation Radiotherapy regimens able to produce the two-thirds reduction in local recurrence seen in these trials, but without long-term hazard, would be expected to produce an absolute increase in 20-year survival of about 24% (except for women at particularly low risk of local recurrence). The average hazard seen in these trials would, however, reduce this 20-year survival benefit in young women and reverse it in older women. ------------------------------------------------------------- Lancet 2000; 355: 175770 ABSTRACT: Is there a life-long risk of brachial plexopathy after radiotherapy of supraclavicular lymph nodes in breast cancer patients? [05/28/2004; Radiotherapy & Oncology] Background and purpose: To contribute to the question whether the risk of radiation-related brachial plexopathy increases, remains constant or decreases with time after treatment. Patients and methods: Between 12/80 and 9/93, 140 breast cancer patients received supraclavicular lymph node irradiation using a telecobalt unit. Total dose was 60 with 3Gy per fraction at a depth of 0.5 cm and 52 with 2.6Gy per fraction to the brachial plexus at a depth of 3 cm. Twenty-eight women received chemotherapy, 34 tamoxifen. Brachial plexopathy was graded using a modified LENT-SOMA score. Actuarial complication-free survival and overall survival were obtained from Kaplan-Meier analysis. The impact of chemotherapy or tamoxifen was tested using the X^2 test. The annual incidence of radiation-related brachial plexopathy was assessed by exponential regression as described by Jung et al. [Radiother Oncol 61 (2001) 233]. Results: Actuarial overall survival was 67.1% after 5 years, 54.0% after 10 years, 49.9% after 15 years, and 44.0% after 20 years. In 19/140 patients, brachial plexopathy grade >=1 occurred after a median interval of 88 (30-217) months. The percentage of patients being free from plexopathy was 96.1% after 5 years, 75.5% after 10 years, 72.1% after 15 years, and 46.0% after 19 years, respectively. A significant impact of type of surgery, chemotherapy or tamoxifen was not observed. The annual incidence of brachial plexopathy was 2.9% for grade>=1 lesions and 0.8% for grade>=3 lesions. The rates did not change significantly with time. Conclusions: The risk of brachial plexopathy after supraclavicular lymph node irradiation in breast cancer patients remains constant for a considerable portion of the patient's life. The full article can be found at: http://dx.doi.org/10.1016/j.radonc.2004.03.005 Link to Medical Treatment Articles Part 2 |
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