Shorter fractionation schedules in breast cancer radiotherapy: Clinical and economic implications

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. 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. 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. The use of accelerated schedules had been resisted until recently by memory of severe late toxicities after hypofractionated schedules based on misapplication of dose algorithms in the 1960s and 1970s. Since then, approximately 8000 patients have been enrolled in five randomised trials testing hypofractionated radiotherapy to the whole breast,