An accumulating body of level I evidence from randomised trials of adjuvant radiotherapy in early breast cancer supports the safety and efficacy of giving a lower total dose in fewer larger fractions (hypofractionation) than the historical standard of 50 Gy in 25 fractions of 2.0 Gy over 5 weeks. 1 Bentzen S.M. Agrawal R.K. Aird E.G. et al. The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet. 2008; 371: 1098-1107 Abstract Full Text Full Text PDF PubMed Scopus (861) Google Scholar , 2 Bentzen S.M. Agrawal R.K. Aird E.G. et al. The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncol. 2008; 9: 331-341 Abstract Full Text Full Text PDF PubMed Scopus (809) Google Scholar , 3 Owen J.R. Ashton A. Bliss J.M. et al. Effect of radiotherapy fraction size on tumour control in patients with early-stage breast cancer after local tumour excision: long-term results of a randomised trial. Lancet Oncol. 2006; 7: 467-471 Abstract Full Text Full Text PDF PubMed Scopus (457) Google Scholar , 4 Whelan T. MacKenzie R. Julian J. et al. Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. J Natl Cancer Inst. 2002; 94: 1143-1150 Crossref PubMed Scopus (554) Google Scholar The published phase 3 trials relate to patients prescribed whole breast radiotherapy, but the principle is being extended to trials evaluating partial breast irradiation restricted to the tumour bed. 5 Orecchia R. Ciocca M. Lazzari R. et al. Intraoperative radiation therapy with electrons (ELIOT) in early-stage breast cancer. Breast. 2003; 12: 483-490 Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar , 6 Vaidya JS, Baum M, Tobias JS, Houghton J. Lancet. Targeted intraoperative radiotherapy; 1999. <http://www.thelancet.com/journals/lancet/misc/protocol/99PRT-47>. Google Scholar , 7 Strnad V, Polgar C. On behalf of the European Brachytherapy Breast Cancer GEC-ESTRO Working Group. GEC-ESTRO APBI Trial: interstitial brachytherapy alone versus external beam radiation therapy after breast conserving surgery for low risk invasive carcinoma and low risk duct carcinoma in-situ (DCIS) of the female breast; 2006. <http://www.apbi.uni-erlangen.de/outline/outline.html>. Google Scholar , 8 Wolmark N, Curran WJ. Trial protocol March 13, 2007. On behalf of NSABP and RTOG of the American College of Radiology (ACR). NSABP Protocol B-39. RTOG Protocol 0413. A randomized phase III study of conventional whole breast irradiation versus partial breast irradiation for women with stage 0, I, or II breast cancer. National surgical adjuvant breast and bowel project (NSABP); 2007. p. 1–132. Google Scholar , 9 OCOG. Ontario Clinical Oncology Group (OCOG), Canadian Institutes of Health Research (CIHR), Canadian Breast Cancer Research Alliance. RAPID: Randomized Trial of Accelerated Partial Breast Irradiation; 2008. <http://clinicaltrials.gov/ct2/show/NCT00282035>. Google Scholar , 10 Yarnold J, Coles C. Trial Protocol, version 4, 19.02.2008. On behalf of the IMPORT LOW Trial Management Group: Intesity Modulated and Partial Organ Radiotherapy. Randomised trial testing intensity modulated and partial organ radiotherapy following breast conservation surgery for early breast cancer. Sutton, Surrey, UK: The Institute of Cancer Research: Royal Cancer Hospital; 2008. p. 1–74. Google Scholar , 11 http://www.irmatrial.it/. Google Scholar Interest in hypofractionation is based not only on the practical advantages to patients and health services of fewer hospital visits, but also on two postulated clinical benefits. The first is that breast cancer is more sensitive to fraction size than formerly thought, so that fewer larger fractions maintain current levels of anti-tumour effect without increasing late adverse effects. The second is that shorter overall treatment times (accelerated hypofractionation) may be more effective in patients with rapidly proliferating tumours.
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