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Background and Purpose: We previously confirmed the efficacy and safety of our technique of whole breast radiation therapy (WBRT) in isocentric lateral decubitus (ILD) position. The purpose of this work is to evaluate the risk factors for long-term fibrosis in patients treated in ILD position. Material and methods: We studies 832 consecutive female patients with early stage BC treated by conservative surgery followed by 3D-conformal WBRT at Institut Curie between 2005 and 2010. Fibrosis and deformation were evaluated at the end of the treatment and subsequently every 6 months during at least 5 years, using NCI CTC v3.0 scale. Different fractionation schedules were used: 66Gy in 33 fractions, 50Gy in 25 fractions, 40Gy in 15 fractions, 41.6Gy in 13 fractions and 30Gy in 5 weekly fractions. Results: Median age is 61.5 years (range: 29 - 90); median follow up is 6.4 years (range: 1.5 - 12.4). During the follow-up, 308 patients (38.9%) had grade 1 fibrosis, and 36 patients (4.3%) only, had grade 2-3 fibrosis. Among patients with grade 1 to 3 fibrosis, the median time to development of fibrosis was 1.6 years (range: 9 days – 8.3 years). In univariate and multivariate analysis, age, cup size and chemotherapy administration had no significant influence on development of breast fibrosis. The hypo fractionated schedule of 30Gy in 5 fractions significantly increased the fibrosis rate (OR=12.5; [2.7; 57.1] p=0.001). On the other hand, 40 Gy/15 fr and 41.6 Gy/13 fr had no significative influence (OR=2.2 [0.5; 11.1] p=0.32) as well as the 66 Gy/33 fr schedule (OR=3.6 [0.8; 15.4] p=0.09) compared to standard scheme of 50 Gy/25 fr. The cosmetic result was good or excellent for 84.8% of cases at the first evaluation. The 30 Gy in 5 fractions schedule significantly influenced the cosmetic result in the multivariate analysis (OR=11.2 [3.1; 43.9]; p Conclusion: Whole breast radiation therapy in ILD position is well tolerated with good cosmesis and low rates of fibrosis, except for the 30 Gy in 5 weekly fractions schedule. Large breast size has a significantly negative influence on cosmetic results and fibrosis. Citation Format: Bronsart E, Dureau S, Xu HP, Costa E, Poortmans P, Chilles A, Berger F, Stilhart A, Fourquet A, Kirova Y. Risk factors for fibrosis after whole breast radiation therapy in lateral position : A large scale single center experience [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-08.