Interest in hypofractionation applied to primary breast cancer was sparked by a review of super/hyperfractionation (fractions 1000 locally advanced or recurrent breast cancer patients irradiated with a range of fractionation regimens ( Figure 1). 1, 2 No better summary exists of the early history of fractionation, including hypofractionation, than that written by Jolian Hendry for a review of UK practices published by the The Royal College of Radiologists in 2006. In the years that followed, Jack Fowler became a leading interpreter of the linear–quadratic model developed by Rodney Withers and colleagues. A few days’ contact with these individuals did more than anything else to stimulate in our student group a lasting interest in clinical radiation biology. My first exposure to Jack Fowler and Oliver Scott was at the Gray Laboratories and Mount Vernon Hospital in June 1975, during the very first Royal College of Radiologists 1 week radiobiology teaching course organised by Hugh Thomlinson for first year trainees. The lower limits of hypofractionation are currently being explored, one approach testing a 5-fraction schedule of local-regional radiotherapy delivered in 1 week. Meanwhile, hypofractionation can be exploited to modulate dose intensity across the breast according to relapse risk by varying fraction size across the treatment volume. A number of concerns relating to the appropriateness of hypofractionation in patient subgroups, including those treated post-mastectomy, advanced local-regional disease and/or to lymphatic pathways are addressed.
15- or 16-fraction schedules are replacing the conventional 25-fraction regimen as a standard of care for adjuvant therapy in an increasing number of countries.
The implication is that there are no advantages in terms of safety or effectiveness of persisting with 2.0 Gy fractions in patients with breast cancer. Four randomised trials testing fraction sizes in the range 2.7–3.3 Gy have reported 10-year follow up in almost 8000 patients, and they provide robust estimates of α/β in the range of 3 Gy. Early indications that breast cancer responds more strongly to fraction size than many other common cancers were followed several decades of investigation, but there is now reliable Level I evidence that this is the case. Conventional fractionation for half a century has been justified on the basis that 2.0 Gy fractions spare dose-limiting late-responding normal tissues to a greater degree than cancerous tissues.
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