Cambridge Breast Intensity Modulated Radiotherapy Trial: dosimetry results for 1,139 patients

Two-dimensional radiotherapy (RT) breast plans can lead to substantial dose inhomogeneity, which may cause increased normal tissue toxicity. We report the dosimetry results of our National Cancer Research Network-adopted randomised trial comparing standard two-dimensional RT with intensity-modulated radiotherapy (IMRT).

Following 3D imaging, a standard plan was produced for all patients. Plans were classified as having significant dose inhomogeneity if they exceeded the upper limit of International Commission on Radiation Units and Measurements Report 50 (>107% of prescribed dose). Those patients with satisfactory dose homogeneity were treated with standard RT. Patients with significant dose inhomogeneity were randomised to standard breast RT or IMRT. The randomised group were replanned with forward-planned IMRT.

A total of 1,145 patients were recruited from March 2003 to July 2007. One patient was randomised in error and therefore excluded. Eight hundred and fourteen out of 1,139 (71%) had significant dose inhomogeneity with standard 2D RT, and were randomised to IMRT or control; 325/1,139 (29%) had acceptable dose homogeneity, and were treated with standard 2D RT. The mean improvement in volumes >107% for IMRT plans was 34 cm³ (P < 0.0001, 95% CI = 26 to 42 cm³). The mean improvement in volumes <95% for IMRT plans was 48 cm³ (P = 0.0001, 95% CI = 34 to 62 cm³).

The mean difference in breast volume between randomised and nonrandomised patients was 596 cm³ (P < 0.0001, 95% CI = 530 to 662 cm³). We aim to report the acute and interim late side effects in spring 2008, if the data are released by the Independent Data Monitoring Committee.

IMRT improves radiotherapy planning, and patients with larger breasts are more likely to require this treatment. However, as there was considerable overlap in the range of breast volumes between the randomised groups, size alone cannot predict the need for IMRT. This trial will quantify the clinical benefit of breast IMRT, in a patient group who consume 30% of RT resources. It will also provide DNA samples linked with high-quality clinical outcome data, for a translational study investigating individual patient variation in normal tissue toxicity. This will bring us closer to the ultimate aim of individualised RT based on a patient's genetic profile.