Abstract DEB2-1: Pro - One Week of Whole Breast RT is the New Standard of Care

Abstract

Abstract “Hypofractionation should not be used unless there is a specific rationale concerning the tumor characteristics of doing so”1. These were the words of Gilbert Fletcher, M.D. Anderson Cancer Center, Texas in 1990. So what prompted this bold statement? In 1969, Frank Ellis published his manuscript proposing an isoeffect formula for hypofractionation with a total dose reduction modelled on acute skin reactions2. The Ellis isoeffect formula was intended to be carefully tested, but there was wholesale international adoption as hypofractionation seemed a perfect solution for constrained radiotherapy resources3. This was coupled with lack of quality assurance for patient positioning, field matching and dose prescription. The perfect solution was in fact the perfect storm with many patients with breast cancer suffering serious late normal tissue toxicity including brachial plexopathy. The linear-quadratic model was described subsequently and separated the distinct fractionation sensitivities of early and late-responding normal tissue4. It became clear that total dose needed to be reduced further as the dose per fraction is increased3. In the early 1980’s, John Yarnold, Royal Marsden Hospital, UK read a research manuscript by Bruce Douglas5, which had a profound effect on him and subsequent UK breast radiation research. It challenged the accepted belief that all tumours respond to radiation fractionation in the same way as early-reacting normal tissues. Yarnold hypothesised that breast cancer is as sensitive to fraction size as late-responding normal tissues and if this is so, 2Gy fractions spare tumour and normal tissues equally. Given this apparent lack of advantage, larger fractions were worth testing. At the same time, other researchers globally started to develop breast cancer hypofractionation clinical trials. This important historical background sets scene for this debate: One week of whole breast radiation is the new standard of care. It demonstrates that there is nothing “new” about breast hypofractionation and that there is certainly a “specific rationale concerning the tumor characteristics” that Fletcher called for. It also highlights our united goal as radiation/clinical oncologists to carefully evaluate and report late normal toxicity so earlier mistakes are not repeated. Breast hypofractionation represents more than 3 decades of high quality international clinical trials underpinned by robust quality assurance6-9. The research has been driven by a strong radiobiological rationale and reduced visits for patients and savings for healthcare systems is a happy consequence. During this debate, I will describe the results of the FAST-Forward trial10, address the postulated concerns and conclude why one week of radiotherapy should be the new standard of care. References1.Fletcher GH. Radiother Oncol, 1991 Jan;20(1):10-5. 2.Ellis F. Clin Radiol. 1969 Jan;20(1):1-7. 3.Yarnold J et al. Int J Radiat Oncol Biol Phys 2011. 1; 79 (1): 1-9. 4.Withers HR et al. Radiother Oncol. 1983 Nov;1(2):187-91. 5.Douglas BG. Int J Radiat Oncol Biol Phys. 1982 Jul;8(7):1143-53. 6.Whelan T et al. J Natl Cancer Inst 94:1143-50, 2002. 7.Whelan TJ et al. N Engl J Med 362:513-20, 2010. 8.Group ST, Bentzen SM et al. Lancet Oncol 9:331-41, 2008. 9.Haviland JS et al. Lancet Oncol 14:1086-1094, 2013. 10.Murray Brunt A et al. Lancet 395:1613-1626, 2020 Citation Format: CE Coles. Pro - One Week of Whole Breast RT is the New Standard of Care [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr DEB2-1.