Changes in radiotherapy fractionation-breast cancer

Abstract

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. 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. 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. 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. 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. 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. Meanwhile, hypofractionation can be exploited to modulate dose intensity across the breast according to relapse risk by varying fraction size across the treatment volume. The lower limits of hypofractionation are currently being explored, one approach testing a 5-fraction schedule of local-regional radiotherapy delivered in 1 week.

Figure 1.

Dose-effect for control of inoperable or recurrent breast cancer, adapted from Cohen. Vertical axis is total dose expressed in Roentgens; Vertical position indicates median tumour dose prescribed. Horizontal axis indicates number of daily fractions given 5-times weekly. Large circles represent published series of minimum 30 patients; open large circles describe control in which ≥50% tumour control; closed large circles describe control in which <50% tumour control. Small circles/dots represent individual patients treated by Cohen; open symbol indicates local control, closed symbol indicates local failure. Dashed line represents the median tumour control dose for 61 of Cohen’s patients. Solid line represents median tumour control doses for previously published series.

Figure 2.

Metaanalysis of tumour control: START pilot, A and B (n = 5861).CI, confidence interval.

Figure 3.

(a) UK IMPORT High Trial schema showing the size and number of fractions to breast and boost subvolumes in three trial groups (n = 2568). (b) IMPORT HIGH equivalent total doses to breast and boost subvolumes based on 2.0 Gy fractions and estimated assuming α/β = 3 Gy.

Figure 4.

(a) UK IMPORT Low Trial schema showing the size and number of fractions to breast and boost subvolumes in three trial groups (n = 2018) radiotherapy. (b) Comparisons of total doses as if delivered using 2.0 Gy fractions (α/β = 3 Gy).

Figure 5.

Timeline of UK Beast RT trials.