Normal tissue complication probability (NTCP) parameters for breast fibrosis: pooled results from two randomised trials

Introduction: the dose–volume effect of radiation therapy on breast tissue is poorly understood. We estimate NTCP parameters for breast fibrosis after external beam radiotherapy.Materials and methods: we pooled individual patient data of 5856 patients from 2 trials including whole breast irradiation followed with or without a boost. A two-compartment dose volume histogram model was used with boost volume as the first compartment and the remaining breast volume as second compartment. Results from START-pilot trial (n?=?1410) were used to test the predicted models.Results: 26.8% patients in the Cambridge trial (5?years) and 20.7% patients in the EORTC trial (10?years) developed moderate-severe breast fibrosis. The best fit NTCP parameters were BEUD3(50)?=?136.4?Gy, ?50?=?0.9 and n?=?0.011 for the Niemierko model and BEUD3(50)?=?132?Gy, m?=?0.35 and n?=?0.012 for the Lyman Kutcher Burman model. The observed rates of fibrosis in the START-pilot trial agreed well with the predicted rates.Conclusions: this large multi-centre pooled study suggests that the effect of volume parameter is small and the maximum RT dose is the most important parameter to influence breast fibrosis. A small value of volume parameter ‘n’ does not fit with the hypothesis that breast tissue is a parallel organ. However, this may reflect limitations in our current scoring system of fibrosi