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© The Author 2006. Published by Oxford University Press.
CORRESPONDENCE |
Re: Survival Effects of Postmastectomy Adjuvant Radiation Therapy Using Biologically Equivalent Doses: A Clinical Perspective
We agree with Gebski et al. (1) that adequate dosage and target area for adjuvant postmastectomy radiation therapy are important for optimal locoregional control. We would, however, disagree with their statement that "it is now generally accepted that the target volume should include the chest wall and the peripheral lymphatics." The Danish trials (2,3) in high-risk premenopausal women and postmenopausal patients have shown a 9%–10% survival benefit from the addition of comprehensive locoregional adjuvant radiation therapy. These large trials dominate category 1 (optimal biological equivalent dose and target volume in the Forest plot in Fig. 3 of Gebski et al.). However, it is well recognized that these trials may have overestimated the degree of benefit from postmastectomy radiation therapy because of inadequate axillary surgery, and so the conclusion that comprehensive regional irradiation is needed in addition to chest wall irradiation is less robust.
There is a presumption that the clinical benefit from radiation therapy is directly proportional to the risk of locoregional recurrence. There is a body of evidence that the critical target for adjuvant radiation therapy is the chest wall. For intermediate-risk disease (i.e., stages IIA and IIB), locoregional recurrence is most common at this site—at which locoregional recurrence is 12% and exceeds that at the supra/infraclavicular region (8%), the axilla (4%), and the internal mammary chain (0.2%) (4). In all category 3 trials (inadequate target volume) analyzed by Gebski et al. (1), irradiation of the chest wall was omitted, supporting our view that this site is the critical target.
In an accompanying editorial, Prosnitz and Marks (5) emphasize the need for quality assurance of adjuvant radiation therapy, the inconclusiveness of data that modern radiation therapy does not increase cardiac mortality, and the potential of molecular profiling to guide the selection of patients for postoperative radiation therapy. The importance of quality control for the radiation therapy delivered has been recognized in recent breast cancer radiation therapy trials (6) [not included in the trials analyzed by Gebski et al. (1)].
These issues are to be addressed by the international Selective Use of Postoperative Radiotherapy After Mastectomy (SUPREMO; BIG 2-04) trial (7) funded by the U.K. Medical Research Council and the European Organisation for Research on Cancer. This trial was designed to evaluate the role of chest wall radiation therapy after mastectomy and a minimum of a level II clearance (minimum of 10 lymph nodes) in women at intermediate risk of locoregional recurrence with one to three involved lymph nodes. The study has a strict radiation therapy quality control protocol. The biological study TRANS-SUPREMO will archive tissue for the whole target population of 3700 patients for future analysis of molecular markers of radiation response/local relapse. The cardiac substudy will evaluate the role of brain natriuretic peptide and other molecular markers in the early detection of cardiac damage from adjuvant radiation therapy and/or contemporary anthracycline-containing regimens. These data will be linked to computed tomography data capturing the volume of the heart irradiated because this volume appears to be a determining parameter for the risk of cardiac damage. Trials such as SUPREMO should be well placed to assess more accurately the benefits in overall survival and risks of cardiac toxicity of adjuvant postmastectomy radiotherapy in this subset of patients for whom the role of postmastectomy radiation therapy is uncertain.
REFERENCES
(1) Gebski V, Lagleva M, Keech A, Simes J, Langlands AO. Survival effects of postmastectomy adjuvant radiation therapy using biologically equivalent doses: a clinical perspective. J Natl Cancer Inst 2006;98:26–38.
(2) Overgaard M, Overgaard J, Rose C, Andersson M, Bach F, Kjaer M, et al. Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy: Danish Breast Cancer Cooperative Group 82b Trial. N Engl J Med 1997;337:949–55.
(3) Overgaard M, Jensen MB, Overgaard J, Hansen PS, Rose C, Andersson M, et al. Postoperative radiotherapy in high-risk postmenopausal breast cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial. Lancet 1999;353:1641–8.[CrossRef][Web of Science][Medline]
(4) Recht A, Gray R, Davidson N, Fowble BL, Solin LJ, Cummings FJ, et al. Loco-regional failure 10 years after mastectomy and adjuvant chemotherapy with or without irradiation: experience of the Eastern Cooperative Oncology Group. J Clin Oncol 1999;17:1689–700.
(5) Prosnitz LR, Marks LB. Postmastectomy radiotherapy: quality counts! J Natl Cancer Inst 2006;98:3–4.
(6) Hurkmans CW, Borger JH, Rutgers EJ, van Tienhoven G. EORTC Breast Cancer Cooperative Group; Radiotherapy Cooperative Group. Quality assurance of axillary radiotherapy in the EORTC AMAROS trial 10981/22023: the dummy run. Radiother Oncol 2003;68:233–40.[CrossRef][Web of Science][Medline]
(7) Kunkler IH, Price A, Dixon JM, Canney P, Prescott R, Sainsbury R, et al. SUPREMO (Selective Use of Postoperative Radiotherapy after Mastectomy—a phase III randomised trial assessing the role of postmastectomy chest wall irradiation in ‘intermediate-risk’ women with operable breast cancer receiving adjuvant systemic therapy [poster abstract 1159]. Proceedings of the International Congress of Radiation Research; 2003 Aug 17–22; Brisbane, Australia.
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J Natl Cancer Inst 2006 98: 1021-1022.
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