Emma J Harris, Mukesh B Mukesh, Ellen M Donovan, Anna M Kirby, Joanne S Haviland, Raj Jena, John Yarnold, Angela Baker, June Dean, Sally Eagle, Helen Mayles, Claire Griffin, Rosalind Perry, Andrew Poynter, Charlotte E Coles, Philip M Evans, On behalf of the IMPORT high trialists

To determine if subsets of patients may benefit from smaller or larger margins when using laser set-up and bony anatomy verification of breast tumour bed boost radiotherapy (RT). Verification imaging data acquired using cone-beam CT, mega-voltage CT or 2D kilovoltage imaging on 218 patients were used (1574 images). Tumour bed (TB) set-up errors for laser only set-up (dlaser) and for bony anatomy verification (dbone) were determined using clips implanted into the TB as a gold standard for the TB position. Cases were grouped by centre, by patient and by treatment related factors, including breast volume, TB position, seroma visibility and surgical technique. Systematic (Σ) and random (σ) TB set-up errors were compared between groups, and tumour bed planning target volume margins (MTB) were calculated. For the study population, Σlaser was between 2.8 and 3.4 mm and Σbone was between 2.2 and 2.6 mm, respectively. Women with larger breasts (p=0.03), easily-visible seroma (p≤0.02) and open surgical technique (p≤0.04) had larger Σlaser. Σbone was larger for women with larger breasts (p=0.015), and lateral tumours (p=0.04). Women with medial tumours (p=0.002) had smaller Σbone. If clips are not used, margins should be 8mm and 10 mm for bony anatomy verification and laser set up, respectively. Individualisation of TB margins may be considered based on breast volume, tumour bed position and seroma visibility. Advances in knowledge: Set-up accuracy using lasers and bony anatomy is influenced by patient and treatment factors. Some patients may benefit from clip-based image guidance more than others.