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

Abstract

SummaryBackground Standard curative schedules of radiotherapy to the breast deliver 25 fractions of 2·0 Gy over 5 weeks. In a randomised trial, we tested whether fewer, larger fractions were at least as safe and as eff ective as standard regimens. In this analysis, we assessed the long-term results of tumour control in the same population.

The impact of dose heterogeneity on late normal tissue complication risk after hypofractionated whole breast radiotherapy

“…Change in photographic breast appearance at 2 years was used to define the late adverse effect caused by radiotherapy in this study. This endpoint has been well established and validated in randomised clinical trials, indicating it to be sensitive to small (<10%) differences in randomised total dose [1][2][3]7,11]. The 2-year timepoint is predictive of the relative effects of randomised groups at longer follow up, even though the absolute rate of adverse effects continues to rise for at least a decade and probably for life [7,22,23].…”

“…Radiotherapy and Oncology 104 (2012) 143-147 The routine use of hypofractionation in breast radiotherapy is supported by outcome data of four large randomised clinical trials in women with early breast cancer [1][2][3][4][5][6][7]. Residual concerns include the impact of dose inhomogeneity on the risk of adverse effects after hypofractionated schedules, so-called 'treble trouble' [8][9][10].…”

Clinical trials in low and middle-income countries — Successes and challenges

“…It is important to have a study that will improve care without increasing complications. Randomized studies in breast cancer have shown that delivery can be given in a shorter period of time without effect on overall survival, local control or toxicities compared to standard fractionation (Haviland et al, 2013, Whelan et al, 2010, Owen et al, 2006). Similar findings are being reported in prostate cancer (Kupelian et al, 2007, Hoffman et al, 2014, Pollack et al, 2013).…”

Hypofractionated Whole-Breast Radiotherapy for Women With Early Breast Cancer: Myths and Realities

“…The underlying cell and molecular processes that explain these differences are not clear, but a mechanistic understanding is not needed to apply the linear-quadratic model safely and effectively. Over the last 20 years, several randomized trials involving a combined total of >7,000 women compared hypofractionated adjuvant radiotherapy to a standard regimen of 50 Gy in 25 fractions (Tables 1 and 2) (14)(15)(16)(17)(18)(19). UK Royal Marsden Hospital/Gloucestershire Oncology Centre (RMH/GOC) and Standardisation of Breast Radiotherapy Trial A (START A) trials tested two dose levels of a 13-fraction regimen in terms of late adverse effects and tumor control; the study design allowed direct estimates of a/b for each trial (15)(16)(17).…”

“…Over the last 20 years, several randomized trials involving a combined total of >7,000 women compared hypofractionated adjuvant radiotherapy to a standard regimen of 50 Gy in 25 fractions (Tables 1 and 2) (14)(15)(16)(17)(18)(19). UK Royal Marsden Hospital/Gloucestershire Oncology Centre (RMH/GOC) and Standardisation of Breast Radiotherapy Trial A (START A) trials tested two dose levels of a 13-fraction regimen in terms of late adverse effects and tumor control; the study design allowed direct estimates of a/b for each trial (15)(16)(17). Based on a combined total of 278 local-regional tumor relapses in the two trials, the adjusted a/b value for tumor control was 4.6 Gy (95% (14,19).…”